ЦИКЛОАЛКАН-1,3-ДИАМИНОВОЕ ПРОИЗВОДНОЕ

Изобретение относится к соединению, представленному общей формулой (1), или его фармацевтически приемлемой соли, которые являются ингибиторами взаимодействия между менином и одним или несколькими белками, выбранными из группы, состоящей из MLL1, MLL2, слитого белка MLL и белка MLL с частичной тандемной дупликацией. В формуле (1) пунктирный круг означает, что кольцо является ароматическим, R1 и R2 представляют собой атом водорода или C1-6 алкильную группу, один из R3 и R4 представляет собой атом водорода, гидроксигруппу, атом галогена, C1-6 алкоксигруппу, ди(C1-6 алкил)карбамоильную группу или оксазолильную группу и другой из R3 и R4 представляет собой атом водорода, гидроксигруппу, атом галогена или C1-6 алкоксигруппу, R5 представляет собой атом водорода, C1-6 алкильную группу или гидрокси C1-6 алкильную группу, R6 представляет собой атом водорода, C1-6 алкильную группу, атом галогена, C1-6 алкоксигруппу, аминогруппу или C1-6 алкиламиногруппу, R7 и R8, взятые вместе с атомом углерода, с ...

ДЕМЕТИЛИРОВАНИЕ ДЛЯ ЛЕЧЕНИЯ ГЛАЗНОГО ЗАБОЛЕВАНИЯ

Группа изоберетний относится к области медицины, а именно к офтальмологии, и предназначена для лечения, облегчения или профилактики возрастного глазного заболевания или патологии. Способ лечения, облегчения или профилактики возрастного глазного заболевания или патологии включает введение субъекту, нуждающемуся в лечении, эффективного количества по меньшей мере одного деметилирующего агента, где деметилирующий агент представляет собой децитабин. Также представлены способы лечения, облегчения или профилактики возрастного глазного заболевания и патологии, включающие повышение уровня фермента ELOVL2 в глазу и/или уровня 22:6(n-3) докозагексаеновой кислоты (ДГК) и 22:5(n-6) докозапентаеновой кислоты (ДПК) в глазу путем введения в глаз эффективного количества мРНК, кодирующей ELOVL2, или генной терапии с использованием вектора экспрессии ELOVL2. В другом воплощении обеспечивается способ, включающий выбор пациента, нуждающегося в лечении возрастного глазного заболевания, и введение в глаз пациента ...

ПЕНТАСАХАРИДНЫЙ КОНЪЮГАТ, СПОСОБ ЕГО ПОЛУЧЕНИЯ И ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ НА ЕГО ОСНОВЕ

Описывается новый пентасахаридный конъюгат формулы (I); в которой R независимо представляет собой SO3-или СН3; вставка представляет гибкую вставку длиной 13-25 атомов; заряд пентасахаридного остатка уравновешен положительно заряженными противоионами; и общее количество сульфатных групп в пентасахаридном остатке составляет 4, 5 или 6. Способ его получения и фармацевтическая композиция на его основе для лечения заболеваний, опосредованных или связанных с тромбином. 3 н. и 6 з.п. ф-лы.

ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ КУПИРОВАНИЯ СИНДРОМА СИСТЕМНОГО ВОСПАЛИТЕЛЬНОГО ОТВЕТА

Изобретение относится к области медицины. Лекарственное средство направлено на купирование синдрома системного воспалительного ответа. Средство содержит, мг: дифосфопиридиннуклеотид 0,3-100 и инозин 40,0-1200. Лекарственное средство может дополнительно содержать ингибитор ангиотензинпревращающего фермента, преимущественно лизиноприл 2,5-100, и сердечный гликозид, преимущественно дигоксин 0,07-0,3. Новое лекарственное средство обладает способностью купировать синдром системного воспалительного ответа независимо от этиологии его возникновения, а также позволяет в короткие сроки получить выраженный и стойкий лечебный эффект. 4 з.п. ф-лы, 4 табл.

СПОСОБЫ КОМБИНИРОВАННОЙ ТЕРАПИИ ДЛЯ ЛЕЧЕНИЯ ПРОЛИФЕРАТИВНЫХ ЗАБОЛЕВАНИЙ

Группа изобретений относится к медицине, а именно к онкологии, и может быть использована для получения лекарственного средства для лечения пролиферативного заболевания у индивидуума. Для этого применяют композицию, содержащую наночастицы таксана и белка-носителя в комбинации с эффективным количеством по меньшей мере одного другого средства, выбранного из децитабина и азацитидина. Причем азацитидин пригоден для перорального введения. Также предложен набор для лечения пролиферативного заболевания. Группа изобретений обеспечивает лечение заболеваний за счет синергетического действия композиции, содержащей наночастицы таксана и белка-носителя в комбинации с децитабином. 2 н. и 39 з.п. ф-лы, 3 табл., 7 ил., 11 пр.

ТВЕРДАЯ ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ, СОДЕРЖАЩАЯ ТЕЛИТРОМИЦИН

Изобретение относится к медицине, в частности к новой твердой фармацевтической композиции телитромицина. Композиция содержит телитромицин или одну из его солей присоединения с фармацевтически приемлемой кислотой в качестве активного вещества и микрокристаллическую целлюлозу в качестве инертного наполнителя, обладающего пластичными свойствами. Изобретение обеспечивает уменьшение размера таблетки телитромицина при равном содержании телитромицина и повышение прочности на разрыв таблетки. 11 з.п. ф-лы, 1 ил., 1 табл.

КОМПОЗИЦИИ СЕЛЕНООРГАНИЧЕСКИХ СОЕДИНЕНИЙ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

Группа изобретений относится к способу лечения диабета и композиции для лечения диабета. Способ лечения диабета включает введение композиции, содержащей комбинацию 5’-Метилселеноаденозина, Se-Аденозил-L-гомоцистеина и Гамма-глутамил-метилселеноцистеина и фармацевтически приемлемый носитель, взятые в определенных концентрациях. Композиция для лечения диабета содержит комбинацию 5’-Метилселеноаденозина, Se-Аденозил-L-гомоцистеина и Гамма-глутамил-метилселеноцистеина и фармацевтически приемлемый носитель, взятые в определенных концентрациях. Группа изобретений обеспечивает создание комбинации соединений селена, эффективной в качестве инсулин-заместительной терапии и в качестве средства, усиливающего действие инсулина, для лечения диабета типа I или типа II. 2 н. и 7 з.п. ф-лы, 38 ил., 1 табл., 7 пр.

Способы и композиции для лечения опухолей

Группа изобретений относится к медицине, а именно к онкологии, и может быть использована для лечения субъекта, страдающего от рака. Для этого применяют комбинацию ингибитора гистондезацетилазы (HDACi) и композицию вакцины, содержащей популяцию плюрипотентных клеток, которые были инактивированы, для получения лекарственного средства для одновременного, раздельного или последовательного введения. Группа изобретений также относится к способу получения популяции плюрипотентных клеток, которые были инактивированы. Использование данной группы изобретений показало, что вакцинация ксеногенными эмбриональными стволовыми клетками в сочетании с ингибитором гистондезацетилазы (вальпроевой кислотой) вызывает более высокий противоопухолевый ответ. 4 н. и 20 з.п. ф-лы, 9 ил., 4 пр.

НОВЫЙ СПОСОБ ИНГИБИРОВАНИЯ РОСТА ВИРУСОВ И/ИЛИ ВИРУЛИЦИДНЫЙ СПОСОБ, И НОВЫЙ АНАЛОГ ПИРАЗИННУКЛЕОТИДА ИЛИ ПИРАЗИННУКЛЕОЗИДА

... 1. Способ ингибирования роста вирусов и/или вирулицидный способ путем воздействия на субъект аналогом пиразиннуклеотида, представленного следующей общей формулой [1], или его солью: где R1 представляет собой атом водорода, или заместитель пиразинового кольца; R2 представляет собой атом водорода, ацильную группу, или карбамоилалкильную или карбоксиалкильную группу, которые могут быть замещены; каждый из R3, R4, R5 и R6, которые могут быть одинаковые или различные, представляет собой атом водорода, или гидроксильную группу, которая может быть замещена или защищена; А представляет собой атом кислорода или метиленовую группу; Y представляет собой атом кислорода или иминогруппу; и n представляет собой целое число от 0 до 3. 2. Способ по п.1, отличающийся тем, что используют аналог пиразиннуклеотида, представленный общей формулой [1], или его соль, где Y представляет собой атом кислорода. 3. Способ по п.1, отличающийся тем, что используют аналог пиразиннуклеотида, представленный общей формулой ...

АНТИТРОМБОЦИТАРНАЯ АКТИВНОСТЬ ОБЩЕГО ЭКСТРАКТА СЕМЯН ACANTHUS MOLLIS И ЕГО СОСТАВЛЯЮЩИЕ

Фармацевтические композиции, содержащие агонист или антагонист аденозинового рецептора

... 1. Применение активного ингредиента, выбранного из группы, состоящей из агониста аденозинового рецептора A3 (A3RAg), агониста аденозинового рецептора A1(A1RAg) и сочетания A3RAg и A1Rag для индуцирования секреции или продуцирования G-CSF. 2. Применение по п.1, где указанным активным ингредиентом является A3RAg. 3. Применение по п.1 или 2, где указанный активный ингредиент представляет собой нуклеотидное производное общей формулы (I) где R1 представляет собой (C1-С10)-алкил, (C1-С10)-гидроксиалкил, (C1-С10)-карбоксиалкил или (C1-С10)-цианоалкил, или группу общей формулы (II) где Y представляет собой атомы кислорода, серы или углерода; X1 представляет собой Н, (C1 -С10)-алкил, RaRbNC(=O)- или HORc-, где Ra и Rb могут быть одинаковыми или разными и выбраны из группы, состоящей из водорода, (C1-С10)-алкила, амино, (C1-С10)-галогеналкила, (C1-С10)-аминоалкила, (C1-С10)-ВОС-аминоалкила и (С3-С10)-циклоалкила, или соединяются вместе с образованием гетероциклического кольца, содержащего два-пять ...

НОВЫЕ ПРОИЗВОДНЫЕ МОРФИНА

... 1. Соединение формулы (А) ! ! где вся (А), за исключением заместителя X, обозначается как MR36G-NR1R2-S; ! R1 представляет собой насыщенную или ненасыщенную (С1-С10)-алкильную группу, линейную или разветвленную, замещенную одной или несколькими ненасыщенностями, причем алкильная цепь может прерываться одним или несколькими гетероатомами, выбранными среди атомов О, S и N; ! R2 представляет собой водород, насыщенную или ненасыщенную (C1-C5)-алкильную группу, линейную или разветвленную, или арил, гетероарил или (C1-C5)-алкиларильную группу; ! R3 представляет собой Y(C=Z)R или группу YR, причем Y и Z представляют собой, независимо, кислород или серу, R представляет собой линейную или разветвленную насыщенную или ненасыщенную (С1-С6)-алкильную группу, при условии, что R3 не является O-СН3; !Х представляет собой водород, радикал -S-R4-W или радикал MR36G-NR1R2-S, ! причем R4 представляет собой (С1-С8)-алкильную группу, насыщенную или ненасыщенную, которая может включать амидные, сложноэфирные ...

АНАЛОГИ ПУРИНОВЫХ НУКЛЕОЗИДОВ ДЛЯ ЛЕЧЕНИЯ FLAVIVIRIDAE, ВКЛЮЧАЯ ГЕПАТИТ С

... 1. Способ лечения организма-хозяина, инфицированного флавивирусом или пестивирусом, включающий введение эффективного количества антипестивирусного или антифлавивирусного биологически активного рибофуранонуклеозида по формуле (I) или его фармакологически приемлемой соли или пролекарства, где R представляет собой H, моно-, ди- или трифосфат, стабилизированный фосфат или фосфонат; X представляет собой O, S[O]n, CH2, CHOH, CH-алкил, CH-алкенил, CH-алкинил, C-диалкил, CH-O-алкил, CH-O-алкенил, CH-O-алкинил, CH-S-алкил, CH-S-алкенил, CH-S-алкинил, NH, N-алкил, N-алкенил, N-алкинил, S(O)N-алкил, S(O)N-алкенил, S(O)N-алкинил, SCH-галоген, или C-(галоген)2, где алкил, алкенил или алкинил может необязательно быть замещенным; n составляет 0-2; так что, когда X представляет собой CH2, CHOH, CH-алкил, CH-алкенил, CH-алкинил, C-диалкил, CH-O-алкил, CH-O-алкенил, CH-O-алкинил, CH-S-алкил, CH-S-алкенил, CH-S-алкинил, CH-галоген или C-(галоген)2; тогда каждый R1 и R1' представляет собой независимо H, OH ...

ПРОИЗВОДНЫЕ ХИНОЛИНА ДЛЯ ПРИМЕНЕНИЯ В ЛЕЧЕНИИ ИЛИ ПРОФИЛАКТИКЕ ВИРУСНОЙ ИНФЕКЦИИ

КОМБИНАЦИЯ ИНГИБИТОРА MCL-1 И СТАНДАРТНОГО ЛЕКАРСТВЕННОГО ПРЕПАРАТА ДЛЯ ЛЕЧЕНИЯ ГЕМАТОЛОГИЧЕСКИХ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙ, ЕЁ ПРИМЕНЕНИЕ И СОДЕРЖАЩИЕ ЕЁ ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ

КОМПОЗИЦИИ СЕЛЕНООРГАНИЧЕСКИХ СОЕДИНЕНИЙ И СПОСОБЫ ИХ ПРИМЕНЕНИЯ

НУКЛЕОЗИДФОСФОРАМИДАТЫ В КАЧЕСТВЕ ПРОТИВОВИРУСНЫХ АГЕНТОВ

VERWENDUNG VON ROXITHROMYCIN ZUR HERSTELLUNG EINES MEDIKAMENTS ZUR VERBESSERUNG DER BIOLOGISCHEN UND ANTIVIRALEN AKTIVITÄT VON PROTEASE-INHIBITOREN

Verwendung von Pyrimidinnukleotiden zur Behandlung von Schädigungen des peripheren Nervensystems

ALKALOIDGLYKOSIDE ZUR VERWENDUNG ALS ARZNEIMITTEL

Tetrahydropyranderivate

Neue Verbindungen der Formel I, DOLLAR F1 worin DOLLAR A T, E, R, R', R'', R·1·, R·2· und R·2'· die in Patentanspruch 1 angegebenen Bedeutungen haben, DOLLAR A eignen sich als Antidiabetika.

The P.I.R. Co. Ltd - business model

Methods of inhibiting fibrogenesis and treating fibrotic disease

The present invention relates to the discovery of an epigenetic relay pathway that controls hepatic stellate cell activation and the wound-healing response in fibrogenesis, including fibrogenesis of the injured liver. Methods of inhibiting fibrogenesis, including liver fibrogenesis and secondary disease states and conditions thereof, and in treating liver damage, including cirrhosis of the liver (which may be caused by viruses or chemicals, including alcohol), are aspects of the present invention. The methods utilize certain nucleoside compounds and/or antibodies which are optionally conjugated. Pharmaceutical compositions represent additional aspects of the invention.

Methods of inhibiting fibrogenesis and treating fibrotic disease

Compositions

There is described a composition comprising an effective amount of a combination of two or more components selected from a NAD precursor; a NAMPT upregulator; a NQO1 upregulator and a NNMT (nicotinamide N-methyltransferase) downregulator.

Treatment for acute myeloid leukaemia

Adjuvants for use in vaccines

Compositions of high viscosity

A respiratory virus deactivating composition in the form of a dry homogenised powder comprising; hydroxypropyl methylcellulose (HPMC) particles; and at least one chemical agent selected from dry powder signillaing agents, wherein the homogenised dry ppwder has a mean viscosity whin the range of 26000 mPa.s ± 2000 mPa.s to 40000 mPs.s ± 5000 mPa.s at 20°C in a 3.6% aqueous solution. The signalling agent may be selected from menthol, strawberry, mint, spearmint, peppermint, eucalyptus, lavender, citrus such as lemon, lime, cumquat, clementine and tangerine, garlic, or combinations thereof; and may make up from 1.5 to ≤7% of the total weight of the composition. The mean viscosity is preferably in the range of 29000 mPa.s ± 5000 mPa.s to 38000 mPs.s ± 5000 mPa.s, particularly, 32900 mPa.s ± 5500 mPa.s. The virus deactivating agent may have activity against coronavirus species selected from SARS-CoV, MERS-Cov, SARS-COV-2, HCov-OC43, CoV-HKU1, HCov-229E; and mutant strains thereof. Use of the ...

Methods and compounds for treating paramyxoviridaevirus infections

Compositions and methods for modulating FXR

Pyrazole compounds as SGLT1 inhibitors

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

COMBINATION THERAPY INCLUDING AN MDM2 INHIBITOR AND ONE OR MORE ADDITIONAL PHARMACEUTICALLY ACTIVE AGENTS FOR THE TREATMENT OF CANCERS

COMPOSITIONS AND METHODS FOR MODULATING FXR

Methods and compounds for treating paramyxoviridaevirus infections

2'-FLUORO SUBSTITUTED CARBA-NUCLEOSIDE ANALOGS FOR ANTIVIRAL TREATMENT

PYRAZOLE COMPOUNDS AS SGLT1 INHIBITORS.

Pyrazole compounds as SGLT1 inhibitors

2'-Chloro nucleoside analogs for hcv infection

CRYSTALLINE FORMS OF ANTIVIRAL SOFOSBUVIR ANALOGUES

Substituted nucleosides, nucleotides and analogs thereof

Methods and compounds for treating paramyxoviridaevirus infections

2'-Fluoro substituted carbanucleoside analogs for antiviral treatment

Compositions and methods for modulating FXR

Methods for treating acute myocardial infarctions and associated disorders.

COMBINATION THERAPY INCLUDING AN MDM2 INHIBITOR AND ONE OR MORE ADDITIONAL PHARMACEUTICALLY ACTIVE AGENTS FOR THE TREATMENT OF CANCERS

2'-Chloro nucleoside analogs for hcv infection

CRYSTALLINE FORMS OF ANTIVIRAL SOFOSBUVIR ANALOGUES

2'-Fluoro substituted carbanucleoside analogs for antiviral treatment

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

2'-Chloro nucleoside analogs for hcv infection

Compositions and methods for modulating FXR

Methods and compounds for treating paramyxoviridaevirus infections

2'-Fluoro substituted carbanucleoside analogs for antiviral treatment

COMBINATION THERAPY INCLUDING AN MDM2 INHIBITOR AND ONE OR MORE ADDITIONAL PHARMACEUTICALLY ACTIVE AGENTS FOR THE TREATMENT OF CANCERS

Pyrazole compounds as SGLT1 inhibitors

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

CRYSTALLINE FORMS OF ANTIVIRAL SOFOSBUVIR ANALOGUES

Methods for treating acute myocardial infarctions and associated disorders.

USE OF LIPOSOMEN WITH SAPONINEN AND STEROLEN IN THE PRODUCTION OF INTRADERMALEN VACCINES

MEDICAL USE OF ZWITTERION CONNECTIONS AS MODULATORS OF THE CFTR - CHANNEL

CONNECTIONS TO THE INHIBITION IAPP ASSOCIATING AMYLOID DEPOSIT

MODIFIED NUCLEOSIDES FOR THE TREATMENT OF VIRUS INFECTIONS AND ABNORMAL ONES OF CELLULAR ONES PROLIFERATION

NEW MORPHINE DERIVATIVES

PYRAZOLDERIVAT, DRUG COMPOSITION, WHICH CONTAIN THIS, AND INTERMEDIATE PRODUCT FOR ITS PRODUCTION

BLOCK COPOLYMER FOR WIRKSTOFFKONJUGATE AND THEIR PHARMACEUTICAL COMPOSITIONS

ANTIVIRAL PYRIMIDINNUKLEOSIDDERIVATE

ALKALOIDGLYKOSIDE FOR USE AS DRUGS

ANTIVIRAL PYRIMIDIN NUCLEOSIDE SIMILAR ONES

Apparatus for controlled delivery of opioid and other medications

A method, system and apparatus for administering various medicaments including those for treating pain and substance dependency are disclosed. The apparatus is a unit for heat activation of a morphine opiate liquid concentrate mixed with a carrier substance to produce inhaled gas. The method includes inhaling the heat activated gaseous vapor concentrate for pain relief, to treat substance dependency or administration of other medicaments. The system includes a heat vaporization unit with security, control and communication capability to provide effective patient care and ensure safety.

Demethylation to treat eye disease

Methods for treating age-related eye diseases or conditions are provided. Methods for treating an age-related eye disease or condition in a subject by administering one or more demethylation compounds or agents are provided.

Methods for treating Filoviridae virus infections

Provided are compounds, methods, and pharmaceutical compositions for treating Filoviridae virus infections by administering ribosides, riboside phosphates and prodrugs thereof, of Formula IV: Formula IV. The compounds, compositions, and methods provided are particularly useful for the treatment of Marburg virus, Ebola virus and Cueva virus infections.

Pharmaceutical composition comprising FLT3 inhibitor and hypomethylating agent for treating acute myeloid leukemia

Provided are a pharmaceutical composition for treatment of acute myeloid leukemia (AML), and a method for treatment of acute myeloid leukemia by using same, the composition comprising an Fms-like tyrosine kinase-3 (FLT3) inhibitor or a pharmaceutically acceptable salt or solvate thereof, and a hypomethylating agent (HMA) or a pharmaceutically acceptable salt or solvate thereof as a therapeutically effective combination.

Methods of treating feline coronavirus infections

Provided are methods of treating feline Coronavirus infections comprising administering a therapeutically effective amount of aza-sugar containing nucleoside analogs or pharmaceutically acceptable salts thereof.

Uridine diphosphate derivatives, prodrugs, compositions and uses thereof

This disclosure relates to the use of uridine diphosphate (UDP) derivatives, salts and/or prodrugs thereof for the treatment of inflammatory conditions (e.g., psoriasis) and glaucoma, to prodrugs of UDP derivatives, compositions comprising therapeutically 5 effective amounts of those prodrugs of the UDP derivatives and methods of using those prodrugs for treating various disorders including, e.g., neuronal disorders, including neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease) and traumatic CNS injury, pain, Down Syndrome (DS), glaucoma, and inflammatory conditions, e.g., psoriasis and rheumatoid arthritis.

Method for treating retinal degeneration with purinergic receptor agonists

Use of A3 adenosine receptor agonist in osteoarthritis treatment

NITROGEN-CONTAINING HETEROCYCIC DERIVATIVES, MEDICINAL COMPOSITIONS CONTAINING THE SAME AND MEDICINAL USE THEREOF

Decitabine derivative formulations

The invention provides derivatives of decitabine with superior chemical stability and shelf life, with similar physiological activity. The derivatives are provided in a non-aqueous formulation, which further stabilizes the derivatives. Methods of treating one or more myelodysplastic syndromes, leukemia, or solid tumours using the formulations are described.

Methods for treating prostate cancer

Disclosed herein are methods and compositions for reducing the recurrence of prostate cancer and for treating prostate cancer.

Combination of an HDAC inhibitor and an antimetabolite

Methods involving PDE4, compositions, and the screening thereof, for the treatment of degenerative ocular pathologies

Biodefenses using triazole-containing macrolides

Vaccine

Combination therapy comprising a TOR kinase inhibitor and a cytidine analog for treating cancer

Provided herein are methods for treating or preventing a cancer, comprising administering an effective amount of a TOR kinase inhibitor and an effective amount of a cytidine analog to a patient having a cancer.

Improving recognition

The invention relates to a composition for use in the treatment or prevention of recognition dysfunction, and/or for improving recognition, in a (prodromal) Alzheimer's patient, in particular in a drug-naive (prodromal) Alzheimer's patient, more particularly in a subject with a mini-mental state examination of 20–30.

2 -alkynyl substituted nucleoside derivatives for treating viral diseases

The present invention relates to 2'-Alkynyl Substituted Nucleoside Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein B, X, R1, R2, R3 and R4 are as defined herein. The present invention also relates to compositions comprising at least one 2'-Alkynyl Substituted Nucleoside Derivative, and methods of using the 2'-Alkynyl Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

Methods of administering glutaminase inhibitors

In some aspects, the invention relates to a method of treating cancer, a myeloproliferative disease, an immunological disease, a neurological disease, or a viral infection, comprising orally administering a compound of formula I, formula II, formula III, formula IV, formula V, and/or formula VI, wherein the compound is administered with a meal (e.g., with food as defined herein) or in fed mode.

Nicotinic acid riboside or nicotinamide riboside compositions, reduced derivatives thereof, and the use thereof

Derivatives of nicotinic acid riboside (NAR), nicotinamide riboside (NR), and reduced NAR and NR, including 1-(2', 3', 5'-triacetyl-beta-D-ribofuranosyl)-1,4-dihydronicotinic acid (4a), and compositions containing the same and/or reduced derivative forms of nicotinamide riboside including 1-(2',3',5'-triacetyl-beta-D-ribofuranosyl)-1,4-nicotinamide (2), are provided for use in the care of treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing one or more NR, NAR, NRH, or NARH derivatives, or prodrugs or salts thereof. In further embodiments, the invention relates to methods of using one or more NR, NAR, NRH, or NARH derivatives, or prodrugs, solvates, or salts thereof, to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival and overall cell and tissue health.

Combination therapy comprising SGLT inhibitors and DPP4 inhibitors

Substituted nucleosides, nucleotides and analogs thereof

Disclosed herein are nucleosides, nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a Filoviridae virus infection with one or more nucleosides and/or nucleotide analogs.

4-(4-(4-phenylureido-naphthalen-1-yl)oxy-pyridin-2-yl)amino-benzoic acid derivative as p38 kinase inhibitor

There is provided a compound of formula I, which compound has antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

4-(4-(4-phenylureido-naphthalen-1-yl)oxy-pyridin-2-yl)amino-benzoic acid derivative as p38 kinase inhibitor

There is provided a compound of formula I, which compound has antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Diaryl urea derivatives as p38 kinase inhibitors

There are provided compounds of formula I, wherein R ...

Substituted-6,8-dioxabicyclo[3.2.1]octane-2,3-diol compounds as targeting agents of ASGPR

Compounds of Formula (A) are described herein and the uses thereof for the treatment of diseases, conditions and/or disorders mediated by pharmaceutical compositions and the uses thereof as asialoglycoprotein receptor (ASGPR) targeting agents.

Compositions comprising nicotinamide riboside and a urolithin

A composition comprising: a)nicotinamide riboside and b)a urolithin which is a compound of formula (I) or a salt thereof: Formula (I) wherein: A, B, C and D are each independently selected from H and OH; W, X and Y are each independently selected from H and OH; and Z is selected from H and OH. The compositions are useful as medicaments, for example for treating muscle-related pathological conditions, neurodegenerative diseases, and/or mitochondrial diseases and as dietary supplements, functional foods and beverages, and specialised nutrition or medical foods.

Method of reducing multi-drug resistance using inositol tripyrophosphate

Inositol trisphosphate (ITPP) causes normalization of tumor vasculature and is a particularly effective cancer therapy when a second chemotherapeutic agent is administered following partial vascularization. ITPP also treats, alone or in combination, multi-drug resistant cancers. ITPP can also be used to reduce the amount of a second chemotherapeutic drug required for anticancer activity. In addition, ITPP enhances immune response and treats hyperproliferative disorders.

Chroman derivatives, medicaments and use in therapy

Novel chroman derivatives and intermediate compounds, compositions containing same, methods for their preparation and uses thereof as therapeutic agents particularly as anti-cancer and chemotherapeutic selective agents are described.

Compositions for treating or preventing obesity and insulin resistance disorders

Provided herein are methods and compositions for modulating the activity or level of a sirtuin, thereby treating or preventing obesity or an insulin resistance disorder, such as diabetes in a subject. Exemplary methods comprise contacting a cell with a sirtuin activating compound or an inhibitory compound to thereby increase or decrease fat accumulation, respectively.

4'-substituted nucleoside derivatives as inhibitors of hcv rna replication

The present invention relates to the use of nucleoside derivatives of formula I wherein B signifies a 9-purinyl residue B1 of formula or a 1-pyrimidyl residue B2 of formula wherein the symbols are as defined in the specification, and of pharmaceutically acceptable salts thereof; for the treatment of diseases mediated by the Hepatitis C Virus (HCV), for the preparation of a medicament for such treatment and to pharmaceutical compositions containing such compounds.

RBM3 in Testicular Cancer Diagnostics and Prognostics

The present disclosure provides a method for determining whether a mammalian subject belongs to a first or a second group, wherein subjects of the first group have a higher risk of having a testicular disorder than subjects of the second group, comprising the steps of: evaluating an amount of RBM3 protein or RBM3 mRNA in at least part of an earlier obtained sample comprising biological material from a testicle of said subject and determining a sample value corresponding to the evaluated amount; comparing said sample value with a predetermined reference value; and if said sample value is higher than said reference value, concluding that the subject belongs to the first group; and if said sample value is lower than or equal to said reference value, concluding that the subject belongs to the second group. Further, a prognostic method for testicular cancer is provided, as well as means and uses with prognostic and diagnostic applications.

Methods of Using C-Met Modulators

Disclosed are methods of treating cancer by administering a compound of Formula I, or a pharmaceutically acceptable salt thereof, in combination with gemcitabine (GEM), or a pharmaceutically acceptable salt thereof, and optionally one or more additional treatments, wherein: R 1 is halo; R 2 is halo; R 3 is (C 1 -C 6 )alkyl; R 4 is (C 1 -C 6 )alkyl; and Q is CH or N.

Estrogen receptor modulators and uses thereof

Described herein are compounds that are estrogen receptor modulators. Also described are pharmaceutical compositions and medicaments that include the compounds described herein, as well as methods of using such estrogen receptor modulators, alone and in combination with other compounds, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

Methods of enhancing drug delivery and effectiveness of therapeutic agents

The present invention in one aspect provides methods of enhancing uptake of a therapeutic agent in a target tissue as well as methods of treating a disease (such as cancer) or enhancing effectiveness of treatment with a therapeutic agent in an individual by co-administering a composition comprising nanoparticles comprising albumin and a poorly water soluble drug such as a taxane with the therapeutic agent. The present invention in another aspect provides a method of treatment or a method of selecting patients for treatment of a disease (such as cancer) with the combination of a therapeutic agent and a composition comprising nanoparticles comprising albumin and a poorly water soluble drug such as a taxane based on one or more characteristics of the target tissue that correlates or indicates the capability of getting enhanced therapeutic agent uptake as a result of the co-administration of the taxane nanoparticle composition in the target tissue (referred to as “the drug uptake capability”). Also provided are pharmaceutical compositions, article of manufacture, and kits useful for methods described herein.

Antiviral transdermal patch and method for producing the same

An antiviral transdermal patch including a backing layer, a viscous polymer layer, and a protection film layer. The viscous polymer layer includes an antiviral agent, a viscous polymer, and a transdermal enhancer. The transdermal enhancer is laurocapram or a mixture thereof. The antiviral agent is a nucleoside antiviral drug with a daily delivery rate of less than 100 mg/day. The patch effectively promotes the penetration of a nucleoside antiviral agent into the blood circulation and avoids enzymolysis in the gastrointestinal tract and the first pass effect of the liver and reduces side effect of drugs, thereby inhibiting the replication of target viruses and reducing viral DNA level in the serum. A method for producing the patch is also provided. The raw materials involved in the invention are easily purchased from the market at a low cost.

COMBINATION OF A NUCLEOSIDE POLYMERASE INHIBITOR WITH A MACROCYCLIC PROTEASE INHIBITOR AND USE THEREOF IN THE TREATMENT OF HEPATITIS C, LIVER FIBROSIS AND IMPAIRED LIVER FUNCTION (as amended)

Embodiments disclosed in the present application relate to a composition that can include a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof. Additional embodiments disclosed relate to methods for treating a disease condition such as a hepatitis C virus infection, liver fibrosis and/or impaired liver function with a hepatitis C viral polymerase inhibitor, or pharmaceutically acceptable salt or prodrug thereof and a hepatitis C viral protease inhibitor, or pharmaceutically acceptable salt or prodrug thereof.

Pentamidine combinations for treating cancer

The present invention relates to the treatment of cancer, e.g., ovarian cancer, breast cancer, pancreatic cancer or colon cancer, with pentamidine and (a) oxaliplatin, (b) gemcitabine, (c) taxol, (d) 5-fluorouracil or (e) CPT 11.

Chroman derivatives, medicaments and use in therapy

Novel chroman derivatives and intermediate compounds, compositions containing same, methods for their preparation and uses thereof as therapeutic agents particularly as anti-cancer and chemotherapeutic selective agents are described.

Nicotyl riboside compositions and methods of use

The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

Glycoside derivatives and uses thereof

This invention relates to compounds represented by formula (I): wherein the variables are defined as herein above, which are useful for treating diseases and conditions mediated by the sodium D-glucose co-transporter (SGLT), e.g. diabetes. The invention also provides methods of treating such diseases and conditions, and compositions etc. for their treatment.

Pharmaceutical compositions of cytidine analogs and methods of use thereof

The present disclosure provides pharmaceutical compositions comprising cytidine analogs for parenteral administration. Also provided are methods of preparing the compositions and methods of treating diseases and disorders using the compositions provided herein.

Methods for transdifferentiation of body tissues

The invention relates to methods for transdifferentiation of body tissues which can be used to generate specific cell types needed for regenerating organs or body parts, following cellular degeneration, injury or amputation. The present invention also describes the use of tissue transdifferentiation for treating cancer and autoimmune disease.

Compounds and pharmaceutical compositions for the treatment of viral infections

Provided herein are compounds, compositions and methods for the treatment of liver disorders, including HCV infections. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Drug Loaded Polymeric Nanoparticles and Methods of Making and Using Same

The present disclosure generally relates to nanoparticles having about 0.2 to about 35 weight percent of a therapeutic agent; and about 10 to about 99 weight percent of biocompatible polymer such as a diblock poly(lactic) acid-poly(ethylene)glycol. Other aspects of the invention include methods of making such nanoparticles.

Certain Compounds, Compositions and Methods

The present invention provides certain tetrahydrouridine derivative compounds, pharmaceutical compositions and kits comprising such compounds, and methods of making and using such compounds.

Treatment of lung cancer

Disclosed are methods of treating lung cancer by administering to a human in need thereof effective amounts of FTS, or various analogs thereof, or a pharmaceutically acceptable salt thereof, optionally, in combination with a chemotherapeutic agent. Chemotherapeutic agents, and combinations thereof, for use with FTS, its analogs, or its salts are also disclosed.

Compounds and methods for treating bacterial infections

The present invention encompasses compounds and methods for treating urinary tract infections.

Local treatment of neurofibromas

A method for treating a neurofibroma, e.g. dermal neurofibroma, a subdermal neurofibroma, or a superficial plexiform neurofibroma, in a subject in need of such treatment is disclosed. The method comprises locally applying a composition to a neurofibroma either topically or intralesionally. This method does not encompass systemic administration of the composition to the subject to have an effect on the neurofibromas. Compositions useful for such treatments and methods of preparing the compositions are disclosed.

Methods and compositions for treating hepatitis c virus

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided.

Hcv combination therapy

Aspects of this invention include methods comprising administering a combination of a Compound (1) below, including particular en crystalline forms thereof and pharmaceutically acceptable salts thereof, with at least one further selected HCV inhibiting compound as described herein for the treatment of Hepatitis C Viral (HCV) infection The methods can be conducted administering the Compound (1) and the at least one further selected HCV inhibiting compound separately or together, including as a regimen of treatment.

Nucleoside phosphoramidate prodrugs

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Treatment of solid tumors with rapamycin derivatives

Rapamycin derivatives have interesting effects in the treatment of solid tumours, optionally in combination with a chemotherapeutic agent.

GPR 119 MODULATORS

Compounds of formula (I) that modulate the activity of the G-protein-coupled receptor GPR119 and their uses in the treatment of diseases linked to the modulation of the G-protein-coupled receptor GPR119 in animals are described herein. 2. A compound according to wherein X is A and Ris —C(O)—O—R.3. A compound according to wherein R claim 1 , R claim 1 , R claim 1 , and R claim 1 , are each hydrogen and Ris C-Ccycloalkyl substituted with C-Calkyl.4. A compound according to wherein Rand Rare each independently hydrogen claim 1 , fluoro claim 1 , or C-Calkyl.5. A compound according to wherein Ris hydrogen and Ris C-Calkyl.6. The compound:Isopropyl 4-{[6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;Isopropyl 4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;Isopropyl 4-{[5-cyano-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;tert-Butyl 4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;1-Methylcyclopropyl 4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;tert-Butyl (3,4-cis)-3-fluoro-4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;1-Methylcyclopropyl (3,4-cis)-3-fluoro-4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;tert-Butyl (3,4-trans)-3-fluoro-4-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}piperidine-1-carboxylate;tert-Butyl (9-anti)-9-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate;1-Methylcyclopropyl (9-anti)-9-{[5-methyl-6-(1-methyl-4,6-dihydropyrrolo[3,4-c]pyrazol-5(1H)-yl)pyrimidin-4-yl]oxy}-3-oxa-7-azabicyclo[3.3.1]nonane-7-carboxylate; ...

Methods for Treating HCV

The present invention features interferon-free therapies for the treatment of HCV. The therapies comprise administering Compound I (or a pharmaceutically acceptable salt thereof) and another anti-HCV agent. Preferably, the therapies are both interferon- and ribavirin-free.

2'-CHLOROACETYLENYL SUBSTITUTED NUCLEOSIDE DERIVATIVES

The present invention relates to 2′-chloroacetylenyl-substituted nucleoside derivatives of the general formula (I): 9. A pharmaceutical composition comprising an inhibitory amount of a compound according to claim 1 , in combination with a pharmaceutically acceptable carrier or excipient.10. A method of treating a viral infection in a subject claim 9 , comprising administering to the subject an inhibitory amount of a pharmaceutical composition according to .11. The method according to claim 10 , wherein the viral infection is hepatitis C virus.12. A method of inhibiting the replication of hepatitis C virus claim 9 , the method comprising supplying a hepatitis C viral NS3 protease inhibitory amount of the pharmaceutical composition of .13. The method of further comprising administering concurrently an additional anti-hepatitis C virus agent.14. The method of claim 11 , wherein said additional anti-hepatitis C virus agent is selected from the group consisting of α-interferon claim 11 , β-interferon claim 11 , ribavarin claim 11 , and adamantine.15. The method of claim 12 , wherein said additional anti-hepatitis C virus agent is an inhibitor of hepatitis C virus helicase claim 12 , polymerase claim 12 , metalloprotease claim 12 , or IRES.16. The pharmaceutical composition of claim 9 , further comprising another anti-HCV agent.17. The pharmaceutical composition of claim 9 , further comprising an agent selected from interferon claim 9 , ribavirin claim 9 , amantadine claim 9 , another HCV protease inhibitor claim 9 , an HCV polymerase inhibitor claim 9 , an HCV helicase inhibitor claim 9 , or an internal ribosome entry site inhibitor.18. The pharmaceutical composition of claim 9 , further comprising pegylated interferon.19. The pharmaceutical composition of claim 9 , further comprising another anti-viral claim 9 , anti-bacterial claim 9 , anti-fungal or anti-cancer agent claim 9 , or an immune modulator.20. The composition of claim 9 , further comprising a cytochrome P450 ...

HEPATITIS C THERAPIES

The invention provides methods for treating hepatitis C viral infections and related viral infections, as well as compounds and compositions that are useful for treating such infections. 2. The compound of wherein R is OR claim 1 , Cl claim 1 , SR claim 1 , NRR claim 1 , aryl or NRNRR.3. The compound of wherein R is hydroxy claim 1 , chloro claim 1 , methoxy claim 1 , mercapto claim 1 , methylthio claim 1 , methylamino claim 1 , isopropylamino claim 1 , propylamino claim 1 , ethylamino claim 1 , dimethylamino claim 1 , cyclopropylamino claim 1 , 2-aminoethylamino claim 1 , 1-(2-hydroxyethyl)hydrazino claim 1 , hydrazino claim 1 , 1-methylhydrazino claim 1 , azetidino claim 1 , pyrrolidino claim 1 , imidazolylpropylamino claim 1 , pyrrolino claim 1 , morpholino claim 1 , piperazino claim 1 , hydroxyethylamino claim 1 , bis-hydroxyethylamino claim 1 , hydroxypropylamino claim 1 , hydroxyethylpyrrolidino claim 1 , or 1-methyl-2-hydroxyethylamino.4. The compound of wherein R is NRR.6. The compound of which is a prodrug.7. The compound of that comprises one or more mono- claim 1 , di- claim 1 , or tri-phosphate groups.8. The compound of that comprises one or more mono-phosphate groups.9. The compound of wherein the compound is a prodrug.10. The compound of wherein one or more phosphorous atoms of the one or more pendent mono- claim 7 , di- claim 7 , or tri-phosphate groups is bonded to one or more alkoxy or aryloxy groups.11. The compound of wherein one or more phosphorous atoms of the pendent mono- claim 7 , di- claim 7 , or tri-phosphate groups is bonded to one or more groups R—O—; wherein each Ris independently a 1-20 carbon branched or unbranched claim 7 , saturated or unsaturated chain claim 7 , wherein one or more of the carbon atoms is optionally replaced with —O— or —S— and wherein one or more of the carbon atoms is optionally substituted with oxo (═O) or thioxo (═S).12. The compound of wherein one or more phosphorous atoms of the one or more pendent mono- claim ...

Kinase protein binding inhibitors

The invention relates to phosphorylation inhibitor compounds and methods of identifying and using them. The invention further relates to pharmaceutical compositions and methods for treating cell proliferative disorders, especially cancer.

COMBINATORIAL THERAPIES FOR THE TREATMENT OF NEOPLASIAS USING THE OPIOID GROWTH FACTOR RECEPTOR

The present invention relates to pharmaceutical compositions for treating neoplasias in an animal or human comprised of a carrier and therapeutically effective amounts of at least one chemotherapeutic agent along with the biotherapeutic endogenous pentapeptide Met-enkephalin, referred to as opioid growth factor. Also provided are methods of treating neoplasias in an animal or human in need of such treatment, comprising the administration to the animal or human therapeutically effective amounts of a pharmaceutical composition comprised of a carrier and therapeutically effective amounts of at least one neoplasia-treating agent, such as a chemotherapeutic agent or radiation, along with opioid growth factor. 1. A pharmaceutical composition for treating neoplasias in an animal or human which are characterized by an opioid growth factor receptor , comprising:therapeutically effective amounts of at least one chemotherapeutic, biotherapeutic, and/or radionuclide agent with between about 20 to 1000 μg/kg body weight of an opioid growth factor; and a carrier.2. The pharmaceutical composition of wherein said agent is a therapeutic agent.3. The pharmaceutical composition of claim 2 , wherein the neoplasias includes not limited to pancreatic cancer claim 2 , squamous cell cancer of the head and neck claim 2 , breast cancer claim 2 , colorectal cancer claim 2 , renal cancer claim 2 , brain cancer claim 2 , prostate cancer claim 2 , bladder cancer claim 2 , bone or joint cancer claim 2 , uterine cancer claim 2 , cervical cancer claim 2 , endometrial cancer claim 2 , multiple myeloma claim 2 , Hodgkin's disease claim 2 , non-Hodgkin's lymphoma claim 2 , melanoma claim 2 , leukemias claim 2 , lung cancer claim 2 , ovarian cancer claim 2 , gastrointestinal cancer claim 2 , Kaposi's sarcoma claim 2 , liver cancer claim 2 , pharyngeal cancer and laryngeal cancer.4. The pharmaceutical composition of claim 3 , wherein the chemotherapeutic agent is selected from but not limited to the ...

Pharmaceutical kit and method for treating cancer

This invention is related to the field of cancer treatment, more specifically to gene therapy in combination with a suitable chemotherapeutic agent. The present invention is related to a new oncolytic virus, which is able to inhibit the growth of malignant tumors or is a treatment of hyperproliferative mammalian cells, or is a treatment of cancer. The oncolytic virus works in combination with a suitable chemotherapeutic agent. More specifically, the present invention provides a pharmaceutical kit comprising an oncolytic adenovirus and a chemotherapeutic agent, and a method for the treatment of cancer. 1. Pharmaceutical kit , comprising: i. binding region;', 'ii. promoter region;', 'iii. insulator region;, 'a. an oncolytic adenovirus, comprising 3 regionsb. a chemotherapeutic agent2. Pharmaceutical kit according to claim 1 , wherein the adenovirus is a serotype 5 adenovirus.3. Pharmaceutical kit according to claim 2 , wherein the binding domain of the serotype 5 adenovirus has been replaced with the binding domain from a serotype 3 adenovirus.4. Pharmaceutical kit according to claim 1 , wherein the promoter region is the promoter of the human Cdc25B gene claim 1 , or a sequence with at least 80% homology.5. Pharmaceutical kit according to claim 4 , wherein the promoter is a fragment of the human Cdc25B gene claim 4 , or a sequence with at least 80% homology.6. Pharmaceutical kit claim 5 , according to claim 5 , wherein the fragment promoter sequence is SEQ ID NO:1 claim 5 , or SEQ ID NO:2 or a sequence with at least 80% homology to SEQ ID NO:1 claim 5 , or at least 80% homology to SEQ ID NO:2.7. Pharmaceutical kit claim 1 , according to claim 1 , wherein the insulator sequence is SEQ ID NO: 3 or a sequence with at least 80% homology to SEQ ID NO:3.8. Pharmaceutical kit claim 1 , according to claim 1 , wherein the oncolytic adenovirus DNA sequence is SEQ ID NO: 4 or a sequence with at least an 80% homology.9. Pharmaceutical kit claim 1 , according to claim 1 , wherein ...

COMPOSITIONS INCLUDING TRICIRIBINE AND TRASTUZUMAB AND METHODS OF USE THEREOF

This application relates to combination therapies including triciribine and related compounds and trastuzumab or a salt thereof and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation. 127-. (canceled)29. The method of claim 28 , wherein the biological sample is taken from breast claim 28 , pancreas claim 28 , ovary claim 28 , colon claim 28 , or rectum.30. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase.31. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase with an antibody.32. The method of claim 28 , wherein the administration is repeated at least twice.33. The method of claim 28 , wherein the administration is repeated at least 4 times.34. The method of claim 28 , wherein at least 10 mg/mof the triciribine compound is administered.35. The method of claim 28 , wherein 10 mg/mor less of the triciribine compound is administered.3614. The method of claim claim 28 , wherein the administration is repeated until regression of the cancer is achieved.37. The method of claim 28 , wherein the drug is administered intravenously.38. The method of claim 28 , wherein the subject has been diagnosed with a carcinoma claim 28 , sarcoma claim 28 , lymphoma claim 28 , leukemia claim 28 , or myeloma.39. The method of wherein the subject is mammal.40. The method of wherein the subject is human.43. The method of claim 28 , wherein at least 100 mg of trastuzumab or a salt thereof is administered.44. The method of claim 28 , wherein at least 200 mg of trastuzumab or a salt thereof is administered.45. The method of claim 28 , wherein at least 400 mg of trastuzumab or a salt thereof is administered. This application is a continuation-in-part of U.S. application Ser. No. 11/096,082, filed ...

COMPOSITIONS INCLUDING TRICIRIBINE AND METHODS OF USE THEREOF

This invention encompasses combination therapies including TCN, TCN-P, TCN-PM and/or related compounds and one or more additional anti-cancer agents, for example, taxanes a molecule that modulates the HER2/neu (erbB2) receptor, anthracyclin compounds, epidermal growth factor receptor inhibitor compounds, one or more platinum compounds and bortezomib and derivatives thereof and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation. 127-. (canceled)29. The composition of claim 28 , wherein the compound of formula I is triciribine.30. The composition of claim 28 , wherein the compound of formula I is triciribine phosphate.31. The composition of claim 28 , wherein the compound of formula I is triciribine phosphonate.32. The composition of claim 28 , wherein the compound of formula I is present in a dose amount of at least 20 mg/m.33. The composition of claim 28 , wherein the compound of formula I is present in an amount of at least 10 mg/m.34. The composition of claim 28 , suitable for parenteral administration.35. The composition of claim 28 , wherein the parenteral administration is intravenous administration.36. The composition of claim 28 , suitable for oral administration.37. The composition of claim 28 , suitable for topical administration.38. The composition of claim 28 , wherein the trastuzumab or a salt thereof is present in an amount from about 1 mg to about 1000 mg.39. The composition of claim 28 , wherein the trastuzumab or a salt thereof is present in an amount from about 100 mg to about 500 mg.40. The composition of claim 28 , wherein the trastuzumab or a salt thereof is present in an amount from about 200 mg to about 450 mg.41. The composition of claim 28 , wherein the trastuzumab or a salt thereof is present in an amount of about 440 mg.42. The composition of claim 28 , wherein the administration of a compound of formula I and trastuzumab is a single ...

INDIBULIN THERAPY

The invention provides combination therapy, wherein one or more other therapeutic agents are administered with indibulin or a pharmaceutically acceptable salt thereof and the combination is synergistic. Another aspect of the invention relates to the treatment of cancer with indibulin as a single agent. Another aspect of the invention relates to dosing regimen for administration of oral dosage forms of indibulin. 1. A method for treating cancer , comprising administering indibulin or a pharmaceutically acceptable salt thereof; and one or more other therapeutic agents , wherein the combination shows efficacy that is greater than the efficacy of either agent being administered alone.2. A method of claim 1 , wherein the indibulin or a pharmaceutically acceptable salt thereof is administered orally.3. A method of claim 1 , wherein the indibulin or a pharmaceutically acceptable salt thereof is administered intravenously.4. A method of claim 1 , wherein the indibulin and the one or more other therapeutic agents are synergistic.5. A method of claim 1 , wherein the indibulin and the one or more other therapeutic agents are additive.6. A method of claim 1 , wherein the other therapeutic agent is selected from erlotinib claim 1 , carboplatin claim 1 , 5-fluorouracil claim 1 , capecitabine claim 1 , paclitaxel claim 1 , tamoxifen claim 1 , vinorelbine claim 1 , cisplatin claim 1 , gemcitabine claim 1 , estramustine claim 1 , doxorubicin claim 1 , vinblastine claim 1 , etoposide claim 1 , and prednisolone.7. A method of claim 1 , wherein the cancer is selected from lung claim 1 , breast claim 1 , ovarian claim 1 , and prostate cancer.8. A method of claim 1 , wherein the compound and the one or more other therapeutic agents are administered simultaneously.9. A method of claim 1 , wherein the one or more other therapeutic agents are administered within about 5 minutes to within about 48 hours prior to or after administration of the compound.10. A method of claim 9 , wherein the ...

COMBINATION THERAPY FOR LYMPHOMA

Methods of treating, preventing or managing lymphomas are disclosed. The methods encompass the administration of an HDAC inhibitor romidepsin and a DNA demethylating agent 5-azacitidine, also known as VIDAZA®. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods provided herein are also disclosed 1. A method of treating lymphoma , said method comprising administering to a patient in need of such treatment a therapeutically effective amount of an HDAC inhibitor and a therapeutically effective amount of a DNA demethylating agent.2. The method of claim 1 , wherein the lymphoma is T-cell lymphoma.3. The method of claim 2 , wherein the T-cell lymphoma is relapsed claim 2 , refractory or resistant to conventional therapy.4. The method of claim 3 , wherein the T-cell lymphoma is cutaneous T-cell lymphoma (CTCL).5. The method of claim 4 , wherein CTCL is refractory or relapsed CTCL.6. The method of claim 1 , wherein the HDAC inhibitor is romidepsin.7. The method of claim 1 , wherein the DNA demethylating agent is 5-azacitidine.8. The method of claim 1 , wherein the HDAC inhibitor is romidepsin in an amount of from about 0.5 to about 28 mg/mper day and the DNA demethylating agent is 5-azacitidine in an amount of from about 10 to 150 mg/mper day.9. The method of claim 8 , wherein 5-azacitidine and romidepsin are administered intravenously.10. The method of claim 8 , wherein the amount of 5-azacitidine is about 50 claim 8 , 75 or 100 mg/mper day.11. The method of claim 8 , wherein the amount of romidepsin is about 8 claim 8 , 10 claim 8 , 12 or 14 mg/mper day.12. The method of claim 1 , wherein the HDAC inhibitor is romidepsin in an amount of from about 10 to about 300 mg/mper day and the DNA demethylating agent is 5-azacitidine in an amount of from about 10 to 150 mg/mper day.13. The method of claim 12 , wherein 5-azacitidine is administered intravenously and romidepsin is administered orally.14. The method of claim 12 , wherein 5- ...

COMPOSITIONS INCLUDING TRICIRIBINE AND EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITOR COMPOUNDS OR SALTS THEREOF AND METHODS OF USE THEREOF

This application relates to combination therapies including triciribine compounds and epidermal growth factor receptor inhibitor compounds, particularly erlotinib-like compounds and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation. 127-. (canceled)29. The method of claim 28 , wherein the biological sample is taken from breast claim 28 , pancreas claim 28 , ovary claim 28 , colon claim 28 , or rectum.30. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase.31. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase with an antibody.32. The method of claim 28 , wherein the administration is repeated at least twice.33. The method of claim 28 , wherein the administration is repeated at least 4 times.34. The method of claim 28 , wherein at least 10 mg/mof the triciribine compound is administered.35. The method of claim 28 , wherein 10 mg/mor less of the triciribine compound is administered.3614. The method of claim claim 28 , wherein the administration is repeated until regression of the cancer is achieved.37. The method of claim 28 , wherein the drug is administered intravenously.38. The method of claim 28 , wherein the subject has been diagnosed with a carcinoma claim 28 , sarcoma claim 28 , lymphoma claim 28 , leukemia claim 28 , or myeloma.39. The method of wherein the subject is mammal claim 28 ,40. The method of wherein the subject is human.43. The composition of claim 28 , wherein the epidermal growth factor receptor inhibitor is gefitinib.44. The composition of claim 28 , wherein the epidermal growth factor receptor inhibitor is erlotinib.45. The composition of claim 28 , wherein the epidermal growth factor receptor inhibitor or salt thereof is present in an amount from ...

Compounds Useful as Inhibitors of ATR Kinase

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; solid forms of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.3. A method for treating cancer in a patient comprising administering a compound of or a pharmaceutically acceptable derivative thereof.4. The method of claim 3 , further comprising administering to said patient an additional therapeutic agent selected from a DNA-damaging agent; wherein said additional therapeutic agent is appropriate for the disease being treated; and said additional therapeutic agent is administered together with said compound as a single dosage form or separately from said compound as part of a multiple dosage form.5. The method of claim 4 , wherein said DNA-damaging agent is selected chemotherapy or radiation treatment.6. (canceled)7. The method of claim 6 , wherein said DNA-damaging agent is selected from ionizing radiation claim 6 , a platinating agent claim 6 , a Topo I inhibitor claim 6 , a Topo II inhibitor claim 6 , an antimetabolite claim 6 , an alkylating agent claim 6 , or an alkyl sulphonates.8. (canceled)9. The method of claim 7 , wherein said platinating agent is selected from Cisplatin claim 7 , Oxaliplatin claim 7 , Carboplatin claim 7 , Nedaplatin claim 7 , Lobaplatin claim 7 , Triplatin ...

Treating Cancer with ATR Inhibitors

This invention relates to methods and compositions for treating pancreatic cancer. More specifically, this invention relates to treating pancreatic cancer with certain ATR inhibitors in combination with gemcitabine and/or radiation therapy. This invention also relates to methods and compositions for treating non-small cell lung cancer. More specifically, this invention relates to treating non-small cell lung cancer with an ATR inhibitor in combination with cisplatin or carboplatin, etoposide, and ionizing radiation. 2. The method of claim 1 , wherein the method increases the sensitivity of pancreatic cancer cells to a cancer therapy selected from gemcitabine or radiation therapy.3. The method of claim 1 , wherein the cancer therapy is gemcitabine.4. The method of claim 1 , wherein the cancer therapy is radiation therapy.5. The method of claim 2 , wherein the pancreatic cancer cells are hypoxic pancreatic cancer cells.7. The method of claim 5 , wherein the cancer therapy is radiation therapy.8. The method of claim 5 , wherein the cancer therapy is gemcitabine.9. The method of claim 2 , wherein the cancer therapy comprises chemoradiation.10. The method of wherein the chemotherapy is gemcitabine.13. The method of wherein the pancreatic cancer cells are derived from a pancreatic cell line selected from PSN-1 claim 12 , MiaPaCa-2 or Panc-1.14. The method of claim 12 , wherein the pancreatic cancer cells are in a cancer patient.1516-. (canceled)18. The method of claim 17 , comprising administering to a patient a compound of formula 821 or 822 in combination with a cancer therapy selected from the group consisting of Cisplatin or Carboplatin claim 17 , Etoposide claim 17 , and ionizing radiation.19. The method of claim 18 , wherein the cancer therapy is Cisplatin or Carboplatin and Etoposide.20. The method of claim 18 , wherein the cancer therapy is Cisplatin or Carboplatin and Etoposide and ionizing radiation.21. The method of claim 18 , wherein the cancer therapy is ...

Agonists of PY2Y Receptor as a Treatment for Aortic Stenosis and Cardiovascular Calcification

The present invention relates to the treatment and/or prevention of aortic valve stenosis (AVS) and valve mineralization. Particularly, the invention provides a target for intervention in the treatment or prevention of AVS through the administration of the P2Yreceptor agonists. Also, the invention provides means to treat hypertension related to decreased arterial compliance and vascular calcification. 2. The assay of claim 1 , wherein said labeled agonist of P2Yreceptor is 2-thioUTP.3. The assay of claim 2 , wherein said 2-thioUTP is labeled in such as way as to enable its detection by spectroscopic claim 2 , photochemical claim 2 , biochemical claim 2 , immunochemical claim 2 , chemical claim 2 , or other physical means.4. The assay according to claim 3 , wherein said 2-thioUTP is labeled with a label selected from the group consisting of: fluorescent dye claim 3 , electron-dense reagent claim 3 , enzyme substrate claim 3 , biotin claim 3 , digoxigenin claim 3 , co-factor claim 3 , ligand claim 3 , chemiluminescent agent claim 3 , radioisotope claim 3 , fluorophore claim 3 , colorimetric hapten claim 3 , enzymatic label claim 3 , and a combination thereof.5. The assay of claim 1 , wherein said displaced P2Yreceptor agonist is selected for further assessing whether it is a compound suitable for the treatment or prevention of aortic stenosis or valve/vascular calcification in a subject.7. The assay according to claim 6 , wherein said 2-thioUTP is labeled with a label selected from the group consisting of: fluorescent dye claim 6 , electron-dense reagent claim 6 , enzyme substrate claim 6 , biotin claim 6 , digoxigenin claim 6 , co-factor claim 6 , ligand claim 6 , chemiluminescent agent claim 6 , radioisotope claim 6 , fluorophore claim 6 , colorimetric hapten claim 6 , enzymatic label claim 6 , and a combination thereof.8. The assay of claim 7 , wherein said radioisotope selected from the group consisting of: I claim 7 , I claim 7 , S claim 7 , C claim 7 , and H ...

COMPOSITIONS INCLUDING TRICIRIBINE AND TAXANES AND METHODS OF USE THEREOF

This application relates to combination therapies including triciribine and related compounds and taxanes and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation. 127-. (canceled)29. The method of claim 28 , wherein the biological sample is taken from breast claim 28 , pancreas claim 28 , ovary claim 28 , colon claim 28 , or rectum.30. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase.31. The method of claim 28 , wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase with an antibody.32. The method of claim 28 , wherein the administration is repeated at least twice.33. The method of claim 28 , wherein the administration is repeated at least 4 times.34. The method of claim 28 , wherein at least 10 mg/mof the triciribine compound is administered.35. The method of claim 28 , wherein 10 mg/mor less of the triciribine compound is administered.3614. The method of claim claim 28 , wherein the administration is repeated until regression of the cancer is achieved.37. The method of claim 28 , wherein the drug is administered intravenously.38. The method of claim 28 , wherein the subject has been diagnosed with a carcinoma claim 28 , sarcoma claim 28 , lymphoma claim 28 , leukemia claim 28 , or myeloma.39. The method of wherein the subject is mammal.40. The method of wherein the subject is human. This application is a continuation-in-part of U.S. application Ser. No. 11/096,082, filed Mar. 25, 2005, which claims the benefit of U.S. provisional patent application No. 60/557,599 filed Mar. 29, 2004, which is incorporated herein by reference.This application relates to combination therapies including triciribine compounds and one or more taxanes and compositions including such combinations with reduced ...

COMPOUNDS USEFUL AS INHIBITORS OF ATR KINASE

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. The compound of claim 1 , wherein{'sub': 1-4', '1-4, 'J is halo, Calkyl, or Calkoxy;'}{'sup': '1', 'sub': 'q', 'Jis —(X)—Y;'}{'sub': 1-6', '1-6', '1-3, 'X is Calkyl wherein 0-2 methylene units of said Calkyl are replaced with NH, O, or S; X is optionally substituted with 1-2 occurrences of Calkyl or halo;'}{'sup': '1', 'sub': '1-3', 'or J and Jjoin together to form a 5-7 heterocyclyl having 1-2 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; wherein the heterocyclyl is optionally substituted with 1 occurrence of halo or Calkyl;'}{'sup': '4', 'Jis CN or L-Z;'}{'sub': '2', 'L is C(O), S(O), or C(O)NR;'}{'sub': t—', '1-6', '1-6, 'Z is (U)Q or Calkyl wherein 0-2 methylene units of said Calkyl are replaced with O or NR;'}{'sub': '1-2', 'U is Calkyl;'}t is 0 or 1;{'sub': '3-6', 'Q is Ccycloalkyl or 4-6 membered saturated or partially saturated heterocyclyl having 1-2 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; and'}{'sub': '1-4', 'R is H or Calkyl.'}3. The compound of claim 2 , wherein{'sup': '4', 'Jis CN or L-Z;'}{'sup': '5', 'Jis H;'}{'sup': '3', 'sub': '1-6', 'Jis Calkyl;'}{'sub': 1-4', '1-3, 'Y is hydrogen, Calkyl, or a 3-6 membered saturated or partially unsaturated heterocyclyl having 1-2 heteroatoms ...

Anti-Viral Pyrimidine Nucleoside Derivatives

A compound for use in the treatment or prophylaxis of viral infections such, for example as chicken pox or shingles caused by the Varicella Zoster virus, said compound having the general formula (II): wherein X is O, S, NH or CH, Y is O, S or NH, Z is O, S or CH, Ris Calkyl, preferably n-alkyl, e.g., n-pentyl or n-hexyl, and one of Rand Ris OH, and the other of Rand Ris a neutral, non-polar amino acid moiety, or a pharmaceutically acceptable salt or hydrate thereof. Said neutral, non-polar amino acid moiety Ror Rmay be (IV): in which R, R, Rand Rare each independently H or Calkyl. In preferred embodiments, one of Ror Ris valine, leucine, isoleucine or alanine, particularly valine. 3. The method of claim 2 , wherein Rand Rare both H.4. The method of claim 1 , wherein one of Ror Ris selected from the group consisting of valine claim 1 , leucine claim 1 , isoleucine and alanine.5. The method of claim 1 , wherein Ror Ris valine.6. The method of claim 5 , wherein said valine is L-valine claim 5 , D-valine or D claim 5 ,L-valine.7. The method of claim 1 , wherein Ris n-alkyl.8. The method of claim 7 , wherein Ris n-pentyl or n-hexyl.9. The method of claim 1 , wherein X claim 1 , Y and Z are all O.12. The method of claim 1 , wherein the viral infection is selected from chicken pox and shingles.13. The method of claim 12 , wherein said viral infection is chicken pox.14. The method of claim 12 , wherein said viral infection is shingles.15. The method of claim 1 , wherein the patient is a human.16. The method of claim 1 , wherein said compound is administered by an oral claim 1 , enteral or parenteral route.17. The method of claim 16 , wherein said compound is administered by an intravenous claim 16 , intramuscular claim 16 , intraperitoneal claim 16 , subcutaneous claim 16 , transdermal claim 16 , airway claim 16 , rectal claim 16 , vaginal claim 16 , or topical route.18. The method of claim 1 , wherein the compound is administered at a dose of 0.001 to 300 mg per kilogram ...

COMPOSITIONS OF BOTANICAL EXTRACTS FOR CANCER THERAPY

Methods and compositions for prevention and therapy of cancer are provided. Compositions comprising therapeutically effective amounts of two or more of an extract of , an extract of and an extract of and optionally a therapeutically effective amount of an extract of are provided. Novel synergistic effects of the use of these compounds in combination therapy are disclosed. Embodiments further comprising therapeutically effective amounts of at least one chemotherapeutic agent are also provided. 153-. (canceled)54Ganoderma lucidumSalvia miltiorrhizaScutellaria barbata. An anticancer composition comprising two or more of an organic extract of , an organic extract of and an organic extract of , wherein each extract comprises a therapeutically effective amount.55Ganoderma lucidumScutellaria barbata.. The composition of claim 54 , wherein the composition comprises about 10 to about 50 percent by weight of the composition the extract of and/or about 10 to about 50 percent by weight of the composition the extract of56Ganoderma lucidum, Salvia miltiorrhizaScutellaria barbata. The composition of claim 54 , wherein the organic extract of claim 54 , or is an ethyl acetate extract claim 54 , an alcohol extract claim 54 , a methylene chloride extract claim 54 , or a methanol extract.57. The composition of claim 54 , wherein the composition displays at least one property selected from the group consisting of: anti-inflammatory activity claim 54 , immunoboosting activity claim 54 , inducing lymphocytes to release TNF-alpha claim 54 , and accelerating cell proliferation.58. The composition of claim 54 , wherein the composition selectively inhibits COX-2 over COX-1.59Hippophae rhamnoides.. The composition of further comprising an extract of60. The composition of further comprising a therapeutically effective amount of at least one chemotherapeutic agent.61. The composition of claim 60 , wherein the chemotherapeutic agent perturbs microtubule polymerization.62. The composition of claim ...

Use of N1,N4-bis[3-(Ethylamino)Propyl]-2-Butene-1,4-Diamine Compounds in Combination with Epigenetic-Acting Pharmaceuticals for Enhanced Cancer Therapy

Combination methods for treatment of cancer and of blood disorders, using PG-11047 ((2Z)-N1,N4-bis[3-(ethy-lammo) propyl]-2-butene-1,4-diamine) and PG-11048 ((2E)-N1,N4-bis[3-(ethylamino)propyl]-2-butene-1,4-diamine) in combination with DNA methyltransferase (DNMT) inhibitors, histone deacetylase (HDAC) inhibitors, or both DNA methyltransferase inhibitors and histone deacetylase inhibitors, are disclosed. Hematopoietic cancers, lung cancers, mesothelioma, cutaneous T-cell lymphoma (CTCL), multiple myeloma, solid tumors, and blood disorders such as myelodysplastic syndromes can be treated using the methods of the invention. 1. A pharmaceutically acceptable composition comprising a combination of PG-11047 ((2Z)-N1 ,N4-bis [3 -(ethylamino)propyl]-2-butene-1 ,4-diamine) or PG-11048 ((2E)-N1 ,N4-bis[3-(ethylamino)propyl]-2-butene-1 ,4-diamine) , and one or more epigenetically-acting drugs.2. The composition of claim 1 , wherein the one or more epigenetically-acting drugs comprise a chemotherapeutic agent.3. The composition of claim 1 , wherein the one or more epigenetically-acting drugs comprise a DNA methyltransferase inhibitor.4. The composition of claim 1 , wherein the one or more epigenetically-acting drugs comprise a histone deacetylase (HDAC) inhibitor.5. The composition of claim 1 , wherein the one or more epigenetically-acting drugs comprise a DNA methyltransferase inhibitor and a histone deacetylase (HDAC) inhibitor.6. The composition of any of claim 1 , additionally comprising one or more additional drugs.7. The composition of claim 6 , wherein the one or more additional drugs comprise one or more chemotherapeutic agents.8. The composition of claim 1 , comprising a combination selected from PG-11047 and 5-azacytidine; PG-11047 and decitabine; PG-11047 and Zebularine; PG-11047 and SGI-110; PG-11047 and RG108; PG-11047 and DZNep; PG-11047 and sodium phenylbutyrate; PG-11047 and valproic acid; PG-11047 and vorinostat; PG-11047 and panobinostat; PG-11047 and ...

METHODS OF USING (+)-1,4-DIHYDRO-7-[(3S,4S)-3-METHOXY-4-(METHYLAMINO)-1-PYRROLIDINYL]-4-OXO-1-(2-THIAZOLYL)-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID FOR TREATMENT OF ANTECEDENT HEMATOLOGIC DISORDERS

Methods of treating, preventing or managing antecedent hematologic disorders, such as myelodysplastic syndrome, including chronic myelomonocytic leukemia are disclosed. The methods encompass the administration of SNS-595. Also provided are methods of treatment using this compound with chemotherapy, radiation therapy, hormonal therapy, biological therapy or immunotherapy. In certain embodiments, the method of treatment comprise administering SNS-595 in combination with cytarabine. Pharmaceutical compositions and single unit dosage forms suitable for use in the methods are also disclosed. 1. A method of treating an antecedent hematological disorder comprising administering to a mammal in need thereof a therapeutically effective amount of an enantiomerically pure (+)-1 ,4-dihydro-7-[(3S ,4S)-3-methoxy-4-(methylamino)-1-pyrrolidinyl]-4-oxo-1-(2-thiazolyl)-1 ,8-naphthyridine-3-carboxylic acid.2. The method of claim 1 , wherein the antecedent hematological disorder is a myelodysplastic syndrome.3. The method of claim 1 , wherein the myelodysplastic syndrome is characterized by ineffective blood cell production claim 1 , progressive cytopenia claim 1 , risk of progression to acute leukemia or cellular marrow with impaired morphology.4. The method of claim 2 , wherein the myelodysplastic syndrome is selected from group consisting of refractory anemia claim 2 , refractory anemia with ringed sideroblasts claim 2 , refractory anemia with excess blasts claim 2 , refractory anemia with excess blasts in transformation claim 2 , and chronic myelomonocytic leukemia.5. The method of claim 2 , wherein the myelodysplastic syndrome is chronic myelomonocytic leukemia.6. The method of claim 5 , wherein the chronic myelomonocytic leukemia is relapsed claim 5 , refractory claim 5 , or resistant to conventional therapy.7. The method of claim 1 , further comprising administering a therapeutically effective amount of a second active agent.8. The method of claim 7 , wherein the second active ...

METHODS OF USE OF CYCLOPAMINE ANALOGS

The invention provides methods for treating various conditions using derivatives of cyclopamine having the following formula: 121-. (canceled)23. The method of claim 22 , wherein Ris H claim 22 , —OR claim 22 , amino claim 22 , sulfonamido claim 22 , sulfamido claim 22 , OC(O)Ror N(R)C(O)R.24. The method of claim 22 , wherein Ris sulfonamido.25. The method of claim 22 , wherein Ris H or heterocycloalkyl.26. The method of claim 25 , wherein Ris H.27. The method of claim 22 , wherein Ris H.28. The method of claim 22 , wherein Ris H claim 22 , alkyl claim 22 , aralkyl claim 22 , —[(W)—C(O)N(R)]Ror —[(W)—N(R)C(O)]R.29. The method of claim 28 , wherein Ris H.30. The method of claim 22 , wherein said compound is epimerically pure.33. The method of claim 32 , wherein the cancer of the hematopoietic system is myeloma claim 32 , leukemia or lymphoma.34. The method of claim 33 , wherein the myeloma is multiple myeloma.35. The method of claim 33 , wherein the leukemia is acute lymphatic leukemia claim 33 , acute myelocytic leukemia claim 33 , chronic myelocytic leukemia or chronic lymphocytic leukemia.36. The method of claim 33 , wherein the lymphoma is non-Hodgkin's lymphoma.37. The method of claim 32 , wherein the cancer of the hematopoietic system is myelodysplastic syndrome.38. The method of claim 32 , wherein the compound is used in combination with one or more other chemotherapeutic agent claim 32 , anti-cancer agent or anti-cancer treatment.39. The method of claim 38 , wherein the chemotherapeutic agent is doxorubicin claim 38 , dexamethasone claim 38 , prednisolone claim 38 , chlorambucil claim 38 , methotrexate claim 38 , vinblastine claim 38 , bortezomib claim 38 , melphalan claim 38 , carmustine claim 38 , cyclophosphamide claim 38 , vincristine claim 38 , lenalidomide claim 38 , thalidomide claim 38 , cytarabine claim 38 , fludarabine or idarubicin.40. The method of claim 38 , wherein the other anti-cancer agent is a corticosteroid or an interferon.41. The method ...

Methods and compositions for treating hepatitis c virus

Disclosed herein is a method of treating a subject infected with hepatitis C virus, said method comprising administering to the subject for a time period an effective amount of GS-7977 and an effective amount of ribavirin. In one aspect, the method comprises administering to the subject an interferon-free treatment regimen comprising an effective amount of GS-7977 and an effective amount of ribavirin. In a particular aspect, the method is sufficient to produce an undetectable amount of HCV RNA in the subject for at least 12 weeks after the end of the time period. Also disclosed herein is a composition useful for the treatment of hepatitis C virus infection, said composition comprising an effective amount of GS-7977 and an effective amount of ribavirin.

Compounds Useful as Inhibitors of ATR Kinase

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 4. The compound of claim 1 , wherein Ring B is phenyl claim 1 , thienyl claim 1 , or morpholinyl.50. The compound of claim claim 1 , wherein Ring B is phenyl or thienyl.6. The compound of claim 5 , wherein m is 0 and n is 1.70. The compound of claim claim 5 , wherein{'sub': 1-6', '1-6, 'X is Calkyl wherein 0-2 methylene units of said Calkyl are replaced with NH or O;'}{'sub': 1-4', '1-3, 'Y is hydrogen, Calkyl, or a 3-7 membered saturated or partially unsaturated heterocyclyl having 1-2 heteroatoms selected from the group consisting of oxygen, nitrogen, and sulfur; wherein the heterocyclyl is optionally substituted with 1 occurrence of halo or Calkyl;'}q is 0 or 1.80. The compound of claim claim 5 , wherein Jis —Calkyl claim 5 , —OH claim 5 , —OCH claim 5 , —CHNHCH claim 5 , —CHOH claim 5 , —OCHCHOH claim 5 , —CHNH-(morpholinyl) claim 5 , or morpholinyl.9. The compound of claim 5 , wherein m is 1 and n is 0.100. The compound of claim claim 5 , wherein J is halo.12. A pharmaceutical composition comprising a compound of and a pharmaceutically acceptable carrier.13. A method for treating cancer in a patient comprising administering a compound of or a pharmaceutically acceptable derivative thereof.140. The method of claim claim 1 , further comprising administering to said ...

Compounds Useful as Inhibitors of ATR Kinase

The present invention relates to compounds useful as inhibitors of ATR protein kinase. The invention also relates to pharmaceutically acceptable compositions comprising the compounds of this invention; methods of treating of various diseases, disorders, and conditions using the compounds of this invention; processes for preparing the compounds of this invention; intermediates for the preparation of the compounds of this invention; and methods of using the compounds in in vitro applications, such as the study of kinases in biological and pathological phenomena; the study of intracellular signal transduction pathways mediated by such kinases; and the comparative evaluation of new kinase inhibitors. 2. The compound of claim 1 , wherein Ring B is phenyl claim 1 , thienyl claim 1 , or morpholinyl.3. The compound of claim 2 , wherein Ring B is phenyl.4. The compound of claim 1 , wherein Jis H claim 1 , CH claim 1 , OH claim 1 , OCH claim 1 , CHOH claim 1 , CHNHCH claim 1 , CHNH-cyclopropyl claim 1 , CH(CHF)NH claim 1 , CH(CH)NH claim 1 , CHNH-(tetrahydrofuranyl) claim 1 , CHNH-(oxetanyl) claim 1 , or piperazinyl.5. The compound of claim 1 , wherein Q is phenyl.6. The compound of claim 5 , wherein p is 0; q is 1; and Jis a Caliphatic group wherein one methylene unit is replaced with S(O).7. The compound claim 6 , wherein Jis —SOCH(CH).9. The compound of claim 8 , wherein Jis H claim 8 , Calkyl; and Jis Calkyl.10. The compound of claim 8 , Jand Jjoin together to form a 3-6 membered fully saturated monocyclic ring having 0-2 heteroatoms selected from the group consisting of oxygen claim 8 , nitrogen claim 8 , and sulfur.11. The compound of claim 8 , wherein Jis hydrogen claim 8 , methyl or ethyl; Jis methyl or ethyl; or Jand Jjoin together to form cyclopropyl claim 8 , cyclobutyl claim 8 , cyclopentyl claim 8 , piperidinyl claim 8 , or tetrahydropyranyl.12. The compound of claim 1 , whereinRing B is phenyl or thienyl;{'sup': 2', '3, 'Jis methyl and Jis methyl;'}{'sup': '4', ...

QUINOLINE DERIVATIVES USED AS PET IMAGING AGENTS

There is provided compounds of formula (I), wherein R, R, X, X, and Xhave meanings given in the description, and pharmaceutically-acceptable salts thereof, which compounds are useful as positron emission tomography (PET) imaging agents, useful in the treatment of diseases in which inhibition of epidermal growth factor receptor tyrosine kinase activity or the inhibition of HER2 activity is desired and/or required, and useful in the treatment of cancer. 2. A compound as claimed in claim 1 , wherein Rrepresents Hetor a Calkyl group optionally substituted by one or more A groups.3. A compound as claimed in claim 1 , wherein A represents —N(R)R.5. A compound as claimed in claim 1 , wherein Rrepresents a C-alkoxy group optionally substituted by one or more halogen atoms claim 1 , or Het.7. A compound as claimed in claim 1 , wherein Xrepresents a halogen claim 1 , ORor SR.9. A compound as claimed in claim 1 , which is selected from the group:{(E)-3-[4-(3-Chloro-4-fluoro-phenylamino)-3-cyano-7-ethoxy-quinolin-6-ylcarbamoyl]-allyl}-prop-2-ynyl-carbamic acid tert-butyl ester;(E)-Pent-2-en-4-ynoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide;(E)-4-[(2-Fluoroethyl)methyl amino]-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinoline-6-yl]amide;(E)-4-[(4-Fluorobenzyl)methylamino]-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinoline-6-yl]amide;(E)-4-{[1-(2-Fluoro-ethyl)-1H-[1,2,3]triazol-4-ylmethyl]-amino}-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide hydrochloride;(E)-N-[4-(3-Chloro-4-fluorophenylamino)-3-cyano-7-ethoxyquinolin-6-yl]-3-[1-(2-fluoro-ethyl)-1H-[1,2,3]triazol-4-yl]-acrylamide;(E)-4-Methylamino-but-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-(2-fluoroethoxy)-quinolin-6-yl]-amide hydrochloride;(E)-4-Prop-2-ynylaminobut-2-enoic acid [4-(3-chloro-4-fluorophenylamino)-3-cyano-7-ethoxy-quinolin-6-yl]-amide hydrochloride;(E)-4-Methylamino- ...

Ratiometric Combinatorial Drug Delivery

The present teachings include ratiometric combinatorial drug delivery including nanoparticles, multi-drug conjugates, pharmaceutical compositions, methods of producing such compositions and methods of using such compositions, including in the treatment of diseases and conditions using drug combinations. 2. The nanoparticle of claim 1 , wherein about 100% of the pharmaceutically active agents contained in the inner sphere are conjugated.3. The nanoparticle of claim 1 , wherein X and Z are independently selected from the group consisting of an antibiotic claim 1 , antimicrobial claim 1 , growth factor claim 1 , chemotherapeutic agent claim 1 , and combinations thereof.4. The nanoparticle of claim 1 , wherein X and Z are independent selected from the group consisting of doxorubicin claim 1 , camptothecin claim 1 , gemicitabine claim 1 , carboplatin claim 1 , oxaliplatin claim 1 , epirubicin claim 1 , idarubicin claim 1 , caminomycin claim 1 , daunorubicin claim 1 , aminopterin claim 1 , methotrexate claim 1 , methopterin claim 1 , dichloromethotrexate claim 1 , mitomycin C claim 1 , porfiromycin claim 1 , 5-fluorouracil claim 1 , 6-mercaptopurine claim 1 , cytosine arabinoside claim 1 , podophyllotoxin claim 1 , etoposide claim 1 , etoposide phosphate claim 1 , melphalan claim 1 , vinblastine claim 1 , vincristine claim 1 , leurosidine claim 1 , vindesine claim 1 , estramustine claim 1 , cisplatin claim 1 , cyclophosphamide claim 1 , paclitaxel claim 1 , leurositte claim 1 , 4-desacetylvinblastine claim 1 , epothilone B claim 1 , docetaxel claim 1 , maytansanol claim 1 , epothilone A claim 1 , combretastatin claim 1 , pharmaceutically active analogs thereof claim 1 , and pharmaceutically acceptable salts thereof.5. The nanoparticle of claim 1 , wherein Y is a pH-sensitive linker.6. The nanoparticle of claim 1 , wherein Y is selected from the group consisting of C-Cstraight chain alkyl claim 1 , C-Cstraight chain O-alkyl claim 1 , C-Cstraight chain substituted alkyl ...

Compositions Containing Resveratrol and Nucleotides

A resveratrol-containing composition capable of providing a therapeutic benefit to a subject such as modulation of a biological activity, improving cell transplantation therapy, or improving macular degeneration or dystrophy treatments. The compositions comprise trans-resveratrol, a metal chelator, one or more additional antioxidants such as quercetin, gamma-tocotrienol, or apple polyphenols, allicin, and nucleotides. 1. A method of administering a supplement , comprising: trans-resveratrol in an amount of about 0.2 to about 2 mg per kg of body weight of the subject,', 'a metal chelating agent in an amount of about 0.5 to about 3 mg per kg of body weight of the subject,', 'one or more nucleotides in an amount of about 0.5 to about 2 mg per kg of body weight of the subject, and', 'one or more additional phenolic antioxidants in a total amount of about 0.05 to about 2 mg per kg of body weight of the subject,, 'administering to a human subject a composition comprising'}wherein said administration is effective to modulate a biological activity in the human subject as compared to administration of resveratrol alone.2. The method of claim 1 , wherein the metal chelating agent comprises phytic acid.3. The method of claim 1 , wherein the one or more additional phenolic antioxidants are selected from the group consisting of apigenin claim 1 , caffeic acid claim 1 , epigallocatechin 3-gallate (EGCG) claim 1 , ferulic acid claim 1 , and quercetin.4. The method of claim 1 , wherein the one or more additional phenolic antioxidants comprises a tocotrienol.5. The method of claim 4 , wherein the tocotrienol is gamma-tocotrienol.6. The method of claim 1 , wherein the one or more additional phenolic antioxidants comprise apple polyphenols.7. The method of claim 1 , wherein the composition further comprises allicin in an amount of about 0.5 to about 2 mg per kg of body weight of the subject.8. A method of treating macular degeneration in a human subject claim 1 , comprising: trans- ...

COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING CANCER BY TARGETING AND INHIBITING CANCER STEM CELLS

The invention relates to compositions and methods for treating cancer comprising administering to a subject in need a pharmaceutically effective dose of a cancer stem cell inhibitor, methods of inhibiting the growth of cancer stem cells or tumor initiating cell comprising administering to a subject in need a pharmaceutically effective dose of a cancer stem cell inhibitor, and methods of enhancing the biological effects of chemotherapeutic drugs or irradiation on cancer cells comprising administering to a subject in need a pharmaceutically effective dose of a chemotherapeutic drug and a pharmaceutically effective dose of a cancer stem cell inhibitor. 1. A method of treating or preventing cancer by targeting and inhibiting cancer stem cells , comprising administering to a subject in need thereof a pharmaceutically effective dose of a cancer stem cell inhibitor.2. The method of claim 1 , wherein the cancer stem cell inhibitor is selected from one or more of rottlerin claim 1 , embelin claim 1 , ellagic acid claim 1 , sulforaphane claim 1 , resveratrol claim 1 , honokiol claim 1 , curcumin claim 1 , diallyltrisulfide claim 1 , quercetin claim 1 , epigallocatechin gallate (EGCG) claim 1 , SAHA claim 1 , m-Carboxycinnamic acid bis-hydroxamine claim 1 , MS-275 claim 1 , SAHA/vornostat claim 1 , m-Carboycinnamic acid bis-hydroxamine claim 1 , benzyl selenocyanate (BSC) claim 1 , benzyl isothiocyanate (BITC) claim 1 , phenyl isothiocyanate (PITC) claim 1 , anthothecol claim 1 , sanguinarine claim 1 , mangostine claim 1 , and 5-aza-2′-deoxycytidine claim 1 , or a pharmaceutically acceptable salt or ester thereof.3. The method of claim 2 , wherein the cancer stem cell inhibitor is rottlerin claim 2 , or a pharmaceutically acceptable salt or ester thereof.4. The method of claim 2 , wherein the cancer stem cell inhibitor is embelin claim 2 , or a pharmaceutically acceptable salt or ester thereof.5. The method of claim 2 , wherein the cancer stem cell inhibitor is sulforaphane ...

COMBINATION THERAPY USING A RUTHENIUM COMPLEX

A combination therapy is disclosed for treating cancer. The method comprises administering to a cancer patient a therapeutically effective amount of trans-[tetrachlorobis(1H-indazole)ruthenate(III)] or a pharmaceutically acceptable salt thereof, and administering to the patient a therapeutically effective amount of one or more other anti-cancer agents as disclosed herein. 1. A method of treating cancer , comprising:administering to a patient in need of treatment, simultaneously or sequentially (1) a pharmaceutically acceptable salt of trans-[tetrachlorobis(1H-indazole)ruthenate(III)], and (2) one or more anti-cancer agents chosen from the group consisting of platinum agents, taxane, anthracyclines, 5-FU and prodrugs thereof, nitrosourea compounds, gemcitabine, temozolomide, EGFR inhibitors, mTOR inhibitors, sorafenib, regorafenib, and sunitinib.2. The method of claim 1 , wherein said pharmaceutically acceptable salt of trans-[tetrachlorobis(1H-indazole)ruthenate(III)] is sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)].3. The method of claim 2 , wherein said one or more anti-cancer agents includes a platinum agent.4. The method of claim 3 , wherein said platinum agent is cisplatin claim 3 , carboplatin claim 3 , or oxaliplatin.5. The method of claim 2 , wherein said one or more anti-cancer agents includes an anthracycline.6. The method of claim 5 , wherein said anthracycline is doxorubicin.7. The method of claim 2 , wherein said one or more anti-cancer agents includes 5-FU or a prodrug thereof.8. The method of claim 2 , wherein said one or more anti-cancer agents includes a nitrosourea compound.9. The method of claim 8 , wherein said nitrosourea compound is BCNU.10. The method of claim 2 , wherein said one or more anti-cancer agents includes gemcitabine.11. The method of claim 2 , wherein said one or more anti-cancer agents includes temozolomide.12. The method of claim 2 , wherein said one or more anti-cancer agents includes an EGFR inhibitor.13. The method ...

THERAPEUTIC COMBINATION COMPRISING A PARP-1 INHIBITOR AND AN ANTI-NEOPLASTIC AGENT

The present invention provides a therapeutic combination comprising (a) a compound of formula (I) as set forth in the specification and (b) one or more antineoplastic agents selected from the group consisting of an alkylating or alkylating-like agent, an antimetabolite agent, a topoisomerase I inhibitor, a topoisomerase II inhibitor, an antimitotic agent and radiation wherein the active ingredients are present in each case in free form or in the form of a pharmaceutically acceptable salt or any hydrate thereof. 2. A combination according to claim 1 , wherein the alkylating or alkylating-like agent is selected from the group consisting of Carboplatin claim 1 , Cisplatin claim 1 , Temozolomide claim 1 , Dacarbazine.3. A combination according to claim 1 , wherein the antimetabolite is Gemcitabine.4. A combination according to claim 1 , wherein the topoisomerase I inhibitor is selected from the group consisting of Irinotecan and Topotecan.5. A combination according to claim 1 , wherein the topoisomerase II inhibitor is nemorubicin.6. A combination according to claim 1 , wherein the antimitotic agent is selected from the group consisting of Paclitaxel and Docetaxel.76. A combination according to claim 1 , wherein in formula (I):{'sub': 1', '2', '1', '2, '(i): when R is hydrogen atom, then Rand Rare both fluorine atoms and, when R is fluorine atom, then Rand Rare both chlorine atoms, fluorine atoms or together form an oxo group (=O), or'}{'sub': 1', '2, '(ii): R is hydrogen atom or fluorine atom, and Rand Rare both fluorine atoms, or'}{'sub': 1', '2, '(iii): R, Rand Rare all fluorine atoms.'}87. A combination according to claim 1 , wherein the compound of formula (I) is selected from the group consisting of:2-[1-(4,4-difluorocyclohexyl)piperidin-4-yl]-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide;2-[1-(4,4-difluorocyclohexy)piperidin-4-yl]-6-fluoro-3 -oxo-2,3-dihydro-1H-isoindole-4-carboxamide;6-fluoro-3-oxo-2-[1-(4-oxocyclohexy)piperidin-4-yl]-2,3-dihydro-1H-isoindole-4- ...

Crystal Forms of Kinase Inhibitors

N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea free base and crystallines form thereof are suitable pharmaceutical ingredients for pharmaceutical compositions useful in the treatment of disease, for example, cancer. 122-. (canceled)24. The method of claim 23 , wherein the solution is administered by a parenteral route.25. The method of claim 23 , further comprising administering 5-azacitidine claim 23 , docetaxel claim 23 , cisplatin claim 23 , or carboplatin.27. The method of claim 26 , wherein the solution is administered by a parenteral route.28. The method of claim 26 , further comprising administering 5-azacitidine claim 26 , docetaxel claim 26 , cisplatin claim 26 , or carboplatin.30. The method of claim 29 , wherein the solid dispersion is administered by an oral route.31. The method of claim 29 , further comprising administering 5-azacitidine claim 29 , docetaxel claim 29 , cisplatin claim 29 , or carboplatin.33. The method of claim 32 , wherein the solid dispersion is administered by an oral route.34. The method of claim 32 , further comprising administering 5-azacitidine claim 32 , docetaxel claim 32 , cisplatin claim 32 , or carboplatin. This application claims priority to U.S. Provisional Application Ser. No. 61/353,058 filed Jun. 9, 2010, which is incorporated by reference in its entirety.The present invention relates to crystalline forms of N-(4-{4-amino-7-[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl}phenyl)-N′-(3-fluorophenyl)urea, processes for preparing the crystalline forms, pharmaceutical formulations thereof, and methods of treating cancer.Mitosis is a process by which a complete copy of a duplicated genome is segregated by the microtuble spindle apparatus into two daughter cells. Aurora-kinases, key mitotic regulators required for genome stability, have been found to be overexpressed in human tumors. There is therefore an existing need in the therapeutic arts for ...

METHODS OF TREATMENT USING COMBINATION THERAPY

Provided herein are methods of treating a proliferative disease in a subject, comprising administering to the subject a therapeutically effective amount of AC220 and a nucleoside analog, a topoisomerase inhibitor or an anthracycline, or a combination thereof. 6. The method of further comprising administering:{'sup': '2', '45 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '50 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '45-60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '70 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '12 mg/m/day of idarubicin for 3 days,'}{'sup': '2', '8 mg/m/day of idarubicin for 2 days, or'}{'sup': '2', '12 mg/m/day of mitoxantrone for 3 days.'}7. The method of further comprising administering:{'sup': '2', '45 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '50 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '45-60 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '70 mg/m/day of daunorubicin for 3 days,'}{'sup': '2', '12 mg/m/day of idarubicin for 3 days,'}{'sup': '2', '8 mg/m/day of idarubicin for 2 days, or'}{'sup': '2', '12 mg/m/day of mitoxantrone for 3 days.'}8. The method of claim 1 , wherein the proliferative disease is leukemia.9. The method of claim 8 , wherein the leukemia is acute myeloid leukemia.10. The method of claim 8 , wherein the leukemia is positive for the FLT3-ITD mutation.11. The method of claim 8 , wherein the mammal is a patient of 65 years or younger with newly diagnosed acute myeloid leukemia.12. The method of claim 2 , wherein the proliferative disease is leukemia.13. The method of claim 12 , wherein the leukemia is acute myeloid leukemia.14. The method of claim 12 , wherein the leukemia is positive for the FLT3-ITD mutation.15. The method of claim 12 , wherein the mammal is a patient of 65 years or younger with newly diagnosed acute myeloid leukemia.16. The method of claim 3 , ...

PYRAZOLE DERIVATIVES

Disclosed are compounds of general formula (I), wherein R, R, R, R, R, R, X, Y, Z, A and B are as defined in the application. 2. The compound of claim 1 , wherein A and B together with carbons to which A and B attach represent optionally substituted aryl or optionally substituted cyclohydrocarbyl.3. The compound of claim 1 , wherein X is oxygen.4. The compound of claim 1 , wherein Y and Z are each nitrogen.5. The compound of claim 1 , wherein Ris selected from the group consisting of hydrogen claim 1 , optionally substituted alkyl and optionally substituted haloalkyl.6. The compound of claim 1 , wherein R is selected from the group consisting of hydrogen claim 1 , optionally substituted alkyl claim 1 , optionally substituted haloalkyl claim 1 , optionally substituted cyclohydrocarbyl and optionally substituted heterocyclyl.7. The compound of claim 1 , wherein R claim 1 , R claim 1 , R claim 1 , Rare independently selected from hydrogen and optionally substituted alkyl.8. The compound of claim 1 , wherein A and B together with carbons to which A and B attach represent phenyl claim 1 , cyclopentyl or cyclohexyl.9. The compound of any one of to claim 1 , wherein R is selected from the group consisting of alkyl claim 1 , phenyl claim 1 , alkylpyrrolidinyl claim 1 , haloalkylpyrrolidinyl claim 1 , cyclohydrocarbyl pyrrolidinyl and alkylpiperidyl.10. The compound of claim 1 , which is selected from the group consisting of(2S,3S,4S,5R,6S)-6-(1,3-dimethyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinoline-5-oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-formic acid;(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(1-isopropyl-3-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinoline-5-oxy)-tetrahydro-2H-pyran-2-formic acid;(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(1-phenyl-3-methyl-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c]isoquinoline-5-oxy)-tetrahydro-2H-pyran-2-formic acid;(2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(3-methyl-1-((R)-1-propylpyrrolidin-2-yl)-6,7,8,9-tetrahydro-3H-pyrazolo[3,4-c] ...

COMBINATION OF ANTI-CTLA4 ANTIBODY WITH DIVERSE THERAPEUTIC REGIMENS FOR THE SYNERGISTIC TREATMENT OF PROLIFERATIVE DISEASES

Compositions and methods are disclosed which are useful of the treatment and prevention of proliferative disorders. 114-. (canceled)15. A method for the treatment of cancer , comprising the administration to a mammal in need thereof a synergistic , therapeutically effective amount of an anti-CTLA-4 antibody with 2′-deoxy-2′ ,2′-difluorocytidine monohydrochloride (β-isomer) , or a pharmaceutically acceptable salt , solvate , or hydrate thereof.16. The method according to claim 15 , wherein the anti-CTLA-4 antibody is selected from the group consisting of: ipilimumab and tremelimumab.17. The method according to claim 15 , wherein said anti-CTLA-4 antibody is ipilimumab.18. The method according to claim 15 , wherein said cancer is a solid tumor.19. The method according to claim 18 , wherein said solid tumor is selected from the group consisting of: lung carcinoma claim 18 , lung metastasis claim 18 , and colon carcinoma.20. The method according to claim 15 , wherein said method is for the treatment of a tumor refractory to said chemotherapeutic agent.21. The method according to claim 15 , wherein said chemotherapeutic agent is administered before the administration of said anti-CTLA4 antibody.22. The method according to claim 15 , wherein said chemotherapeutic agent is administered essentially simultaneously with the administration of said anti-CTLA4 antibody.23. The method according to claim 15 , wherein said cancer treatment further comprises an anti-proliferative cytotoxic agent either alone or in combination with radiation therapy.24. The method according to claim 23 , wherein said anti-proliferative cytotoxic agent is cisplatin.25. The method according to claim 23 , wherein said anti-proliferative cytotoxic agent is paraplatin.26. The method according to claim 15 , wherein said chemotherapeutic agent is administered at a dose of about 200 mg.27. The method according to claim 15 , wherein said chemotherapeutic agent is administered at a dose of about 1 g.28. The ...

FIXED DOSING OF HER ANTIBODIES

The present invention concerns fixed dosing of HER antibodies, such as Pertuzumab. 1. A method for treating cancer comprising administering one or more fixed dose(s) of a HER antibody to a human patient in an amount effective to treat the cancer.2. The method of wherein the antibody binds to a HER receptor selected from the group consisting of EGFR claim 1 , HER2 claim 1 , and HER3.3. The method of wherein the antibody binds to HER2.4. The method of wherein the HER2 antibody binds to Domain II of HER2 extracellular domain.5. The method of wherein the antibody binds to a junction between domains I claim 1 , II and III of HER2 extracellular domain.6. The method of wherein the HER antibody inhibits heterodimerization of HER2 with EGFR or HER3.7. The method of wherein the HER antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4 claim 1 , respectively.8. The method of wherein the HER antibody is pertuzumab.9. The method of wherein the fixed dose is in the range from about 20 mg to about 2000 mg of the HER antibody.10. The method of wherein the fixed dose is selected from the group consisting of approximately 420 mg claim 9 , approximately 525 mg claim 9 , approximately 840 mg claim 9 , and approximately 1050 mg of the HER antibody.11. The method of wherein the fixed dose is 420 mg of the HER antibody.12. The method of wherein the fixed dose is 840 mg of the HER antibody.13. The method of wherein the fixed dose is 1050 mg of the HER antibody.14. The method of wherein the fixed dose is 525 mg of the HER antibody.15. The method of wherein a fixed dose of the HER antibody is administered to the patient approximately every week claim 1 , approximately every 2 weeks claim 1 , approximately every 3 weeks claim 1 , or approximately every 4 weeks.16. The method of wherein a fixed dose of the HER antibody is administered to the patient approximately every 3 weeks.17. The method of comprising administering a loading dose of ...

Cancer Treatment Method

The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines and at least one additional anti-neoplastic compound. In particular, the method relates to a methods of treating cancers by administration of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine and salts and solvates thereof in combination with at least one additional anti-neoplastic compound. 1(i) a compound of formula (I″). A method of treating gastric cancer in a mammal, comprising: administering to said mammal therapeutically effective amounts of(ii) oxaliplatin, and(iii) capecitabine. This application is filed as a continuation application of U.S. application Ser. No. 13/209,889 filed Aug. 15, 2011, and U.S. application Ser. No. 12/516,661 filed May 28, 2009, now abandoned, which is a National Phase Application of International Application No. PCT/US2007/84215 filed Nov. 9, 2007, which claims priority from U.S. Provisional Application Nos. 60/867,431 filed Nov. 28, 2006; 60/943,662 filed Jun. 13, 2007; and 60/951,271 filed Jul. 23, 2007.The present invention relates to a method of treating cancer in a mammal by administration of 4-quinazolinamines in combination with other anti-neoplastic compounds. In particular, the method relates to methods of treating cancers by administration of a combination of N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine or salts or solvates thereof along with additional anti-neoplastic compounds.Effective chemotherapy for cancer treatment is a continuing goal in the oncology field. Generally, cancer results from the deregulation of the normal processes that control cell division, differentiation and apoptotic cell death. Apoptosis (programmed cell death) plays essential roles in embryonic development and pathogenesis of various diseases, such as degenerative neuronal diseases, ...

METHODS AND COMPOSITIONS FOR TREATING HEPATITIS C VIRUS

A method and composition for treating a host infected with hepatitis C comprising administering an effective hepatitis C treatment amount of a described 1′, 2′ or 3′-modified nucleoside or a pharmaceutically acceptable salt or prodrug thereof, is provided. 2. The method of claim 1 , wherein Rand Rare each independently H; phosphate; a stabilized phosphate prodrug; acyl; or a pharmaceutically acceptable leaving group which claim 1 , when administered in vivo claim 1 , provides a compound wherein Rand Rare each independently H or phosphate.3. The method of claim 1 , wherein Ris hydrogen claim 1 , acyl claim 1 , or phosphate.4. The method of claim 1 , wherein Ris hydrogen or phosphate.5. The method of claim 1 , wherein Ris phosphate.6. The method of claim 1 , wherein Ris hydrogen or acyl.7. The method of claim 1 , wherein Ris hydrogen.8. The method of claim 1 , wherein Ris alkyl.9. The method of claim 1 , wherein Ris methyl.10. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —C(O)O(alkyl) claim 1 , —C(O)O(lower alkyl) claim 1 , —O(acyl) claim 1 , —O(lower acyl) claim 1 , —O(alkyl) claim 1 , —O(lower alkyl) claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).11. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , alkyl claim 1 , azido claim 1 , cyano claim 1 , alkenyl claim 1 , alkynyl claim 1 , Br-vinyl claim 1 , —O(alkenyl) claim 1 , chloro claim 1 , bromo claim 1 , iodo claim 1 , NO claim 1 , NH claim 1 , —NH(lower alkyl) claim 1 , —NH(acyl) claim 1 , —N(lower alkyl) claim 1 , or —N(acyl).12. The method of claim 1 , wherein Rand Rare each independently hydrogen claim 1 , OR claim 1 , hydroxy claim 1 , azido claim 1 , cyano ...

THERAPEUTIC AGENTS FOR PANCREATIC CANCER

We achieved the present invention on the basis of the finding that an excellent therapeutic effect against pancreatic cancer can be obtained by administering an XL-6 inhibitor and an antimetabolite to pancreatic cancer patients. We also found that metastatic lesions from human pancreatic cancer can be reduced and ascites can be eliminated. 1. A therapeutic composition for pancreatic cancer comprising an IL-6 inhibitor , said composition further comprising an antimetabolite or being administered in combination with an antimetabolite.2. The therapeutic composition of wherein the IL-6 inhibitor is a substance binding to the IL-6 receptor.3. The therapeutic composition of wherein the substance binding to the IL-6 receptor is an anti-IL-6 receptor antibody.46. The therapeutic composition of wherein the anti-IL- receptor antibody is a chimeric antibody claim 3 , a humanized antibody or a human antibody.5. The therapeutic composition of wherein the antimetabolite is a cytosine analog.6. The therapeutic composition of wherein the cytosine analog is gemcitabine or a salt thereof.7. The therapeutic composition of wherein gemcitabine or a salt thereof is gemcitabine hydrochloride.8. A method for treating pancreatic cancer comprising the step of administering an IL-6 inhibitor and an antimetabolite to a subject.9. The method of wherein the IL-6 inhibitor is a substance binding to the IL-6 receptor.10. The method of wherein the substance binding to the IL-6 receptor is an anti-IL-6 receptor antibody.11. The method of wherein the anti-IL-6 receptor antibody is a chimeric antibody claim 10 , a humanized antibody or a human antibody.12. The method of wherein the antimetabolite is a cytosine analog.13. The method of wherein the cytosine analog is gemcitabine or a salt thereof.14. The method of wherein gemcitabine or a salt thereof is gemcitabine hydrochloride.15. An IL-6 inhibitor for use in a method for treating pancreatic cancer by administering it in combination with an ...

Compositions and Methods for Treatment of Cancer

The present invention relates to pyrroloquinolinyl-pyrrolidine-2,5-dione compounds in combination with chemotherapeutic agents. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a pyrroloquinolinyl-pyrrole-2,5-dione compound or pyrroloquinolinyl-pyrrolidine-2,5-dione compound of the present invention and also administering a effective amount of a chemotherapeutic agent. 115-. (canceled)1716. The pharmaceutical composition of , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen , raloxifene , anastrozole , exemestane , letrozole , trastuzumab , imatinib , paclitaxel , cyclophosphamide , lovastatin , mimosine , gemcitabine , araC , 5-fluorouracil , methotrexate , docetaxel , goserelin , vinctristine , vinblastine , nocodazole , teniposide , etoposide , gemcitabine , epothilone , navelbine , camptothecin , daunorubicin , dactinomycin , mitoxantrone , amsacrine , doxorubicin , epirubicin or idarubicin.1826-. (canceled)28. The method of claim 27 , wherein said second chemotherapeutic agent is selected from the group consisting of tamoxifen claim 27 , raloxifene claim 27 , anastrozole claim 27 , exemestane claim 27 , letrozole claim 27 , trastuzumab claim 27 , imatinib claim 27 , paclitaxel claim 27 , cyclophosphamide claim 27 , lovastatin claim 27 , mimosine claim 27 , gemcitabine claim 27 , araC claim 27 , 5-fluorouracil claim 27 , methotrexate claim 27 , docetaxel claim 27 , goserelin claim 27 , vinctristine claim 27 , vinblastine claim 27 , nocodazole claim 27 , teniposide claim 27 , etoposide claim 27 , gemcitabine claim 27 , epothilone claim 27 , navelbine claim 27 , camptothecin claim 27 , daunorubicin claim 27 , dactinomycin claim 27 , mitoxantrone claim 27 , amsacrine claim 27 , doxorubicin claim 27 , epirubicin or idarubicin.29. The method of wherein said treating said cell proliferative ...

Neutralization of flt3 ligand as a leukemia therapy

Disclosed herein are methods and compositions for treating leukemia and preventing leukemia relapse related to the administration of agents that inhibit the binding of FLT3 ligand to FLT3.

NOVEL GLYCOSIDE COMPOUNDS

Compounds of formula (I): 2. The compound of claim 1 , wherein Y is halo and Z is aryl substituted with C-Calkoxyl or C-Ccycloalkyl.6. The compound of claim 4 , wherein X is RC(O)NHCH— or RC(O)NHNHCH— claim 4 , Y is H or halo claim 4 , and Z is aryl substituted with C-Ccycloalkyl.9. The compound of claim 7 , wherein Y is H or halo claim 7 , and Z is unsubstituted aryl or aryl substituted with C-Ccycloalkyl.11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .12. A method of treating a disorder related to sodium-dependent glucose co-transporter 2 claim 1 , comprising administering to a subject in need thereof an effective amount of a compound of .13. The method of claim 12 , wherein the disorder is type 1 diabetes mellitus claim 12 , type 2 diabetes mellitus claim 12 , or hyperglycemia.14. The method of claim 12 , further comprising administering to the subject an antidiabetic agent claim 12 , an anti-obesity agent claim 12 , an anti-diabetic complications agent claim 12 , an antihypertensive agent claim 12 , an antiplatelet agent claim 12 , an anti-atherosclerotic agent claim 12 , or a hypolipidemic agent.15. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of .16. A method of treating a disorder related to sodium-dependent glucose co-transporter 2 claim 5 , comprising administering to a subject in need thereof an effective amount of a compound of .17. The method of claim 16 , wherein the disorder is type 1 diabetes mellitus claim 16 , type 2 diabetes mellitus claim 16 , or hyperglycemia.18. The method of claim 16 , further comprising administering to the subject an antidiabetic agent claim 16 , an anti-obesity agent claim 16 , an anti-diabetic complications agent claim 16 , an antihypertensive agent claim 16 , an antiplatelet agent claim 16 , an anti-atherosclerotic agent claim 16 , or a hypolipidemic agent.19. A pharmaceutical composition comprising a pharmaceutically ...

2'-FLUORONUCLEOSIDES

2′-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: 147.-. (canceled)48. A method for the treatment of a HCV infection in a host in need thereof comprising administering an effective treatment amount of a β-D-2′-fluoronucleoside wherein the 2′-fluoro of the β-D-2′-fluoronucleoside is alpha (α) , or a pharmaceutically acceptable salt or prodrug thereof , optionally in a pharmaceutically acceptable carrier or diluent.49. The method of claim 48 , wherein the β-D-2′-fluoronucleoside has a pyrimidine base.50. The method of claim 49 , wherein the pyrimidine base is selected from the group consisting of thymine claim 49 , uracil claim 49 , 5-halouracil claim 49 , 5-fluorouracil claim 49 , cytosine claim 49 , 5-fluorocytosine claim 49 , 5-methylcytosine claim 49 , 6-aza-pyrimidine claim 49 , 6-azacytosine claim 49 , 2- and/or 4-mercaptopyrmidine claim 49 , C-alkylpyrimidine claim 49 , C-benzylpyrimidine claim 49 , C-halopyrimidine claim 49 , C-vinylpyrimidine claim 49 , C-acetylenic pyrimidine claim 49 , C-acyl pyrimidine claim 49 , C-hydroxyalkyl purine claim 49 , C-amidopyrimidine claim 49 , C-cyanopyrimidine claim 49 , C-nitropyrimidine claim 49 , and C-aminopyrimidine.51. The method of claim 49 , wherein the pyrimidine base is thymine.52. The method of claim 49 , wherein the pyrimidine base is uracil.53. The method of claim 49 , wherein the pyrimidine base is 5-halouracil.54. The method of claim 49 , wherein the pyrimidine base is cytosine.55. The method of claim 49 , wherein the pyrimidine base is 5-fluorocytosine.56. The method of claim 48 , wherein the β-D-2′-fluoronucleoside has a purine base.57. The method of claim 56 , wherein the purine base is selected from the group consisting of N-alkylpurine claim 56 , N-acylpurine (wherein acyl is C(O)(alkyl claim 56 , aryl claim 56 , ...

Compositions including triciribine and bortezomib and derivatives thereof and methods of use thereof

This application relates to combination therapies including triciribine and related compounds and bortezomib and derivatives thereof analogs and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.

CONCENTRATION-ENHANCING DRINK

A concentration-enhancing drink contains, in each case independently of one another, per liter: 1 mg to 10 g, preferably 1 to 1000 mg, still more preferably 10 to 500 mg, in particular 50 to 300 mg, of epigallocatechin gallate; 1 to 500 mg, preferably 10 to 100 mg, in particular 20 to 80 mg, of nicotinamide ribose; and/or 0.05 to 10 g, preferably 0.1 to 5 g, in particular 0.5 to 3 g of tryptophan. 112-. (canceled)13. A drink , comprising , per liter:1 mg to 10 g epigallocatechin gallate; and1 to 500 mg nicotinamide-ribose, and/or 0.05 to 10 g tryptophan.14. The drink according to claim 13 , wherein the epigallocatechin gallate is present in an amount from 1 to 1000 mg claim 13 , and/or the nicotinamide-ribose is present in an amount from 10 to 100 mg claim 13 , and/or the tryptophan is present in an amount from 0.1 to 5 g.15. The drink according to claim 13 , wherein the epigallocatechin gallate is present in an amount from 10 to 500 mg claim 13 , and/or the nicotinamide-ribose is present in an amount from 20 to 80 mg claim 13 , and/or the tryptophan is present in an amount from 0.5 to 3 g.16. The drink according to claim 13 , wherein the epigallocatechin gallate is present in an amount from 50 to 300 mg.17. The drink according to claim 13 , further comprising an amount of stevioside.18. The drink according to claim 17 , wherein the stevioside is present in an amount from 0.1 to 500 mg.19. The drink according to claim 17 , wherein the stevioside is present in an amount from 1 to 100 mg.20. The drink according to claim 13 , present in volume from 100 ml to 2 liters.21. A drink base claim 13 , comprising a mixture of components forming a base which claim 13 , upon the addition of a liquid selected from the group consisting of water claim 13 , mineral water claim 13 , and fruit juice forms the drink according to .22. The drink base according to claim 21 , where said mixture is present in solid form.23. The drink base according to claim 22 , where said mixture is in ...

Diagnostic, Prognostic and Therapeutic Uses of miRs in Adaptive Pathways and Disease Pathways

Described herein are methods and compositions for the diagnosis, prognosis and treatment of various adaptive and/or disease pathways by examining samples containing one or more miRs therein, and by formulating therapeutic agents therefrom.

METHOD TO IDENTIFY A PATIENT WITH AN INCREASED LIKELIHOOD OF RESPONDING TO AN ANTI-CANCER THERAPY

The invention provides methods for identifying patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist. The invention also provides methods for monitoring a patients' response to the anti-cancer therapy. The invention also provides kits and articles of manufacture for use in the methods. 1. A method of identifying a patient who may benefit from treatment with an anti-cancer therapy comprising a VEGF antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient may benefit from treatment with the anti-cancer therapy.2. A method of predicting responsiveness of a patient suffering from cancer to treatment with an anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient is more likely to be responsive to treatment with the anti-cancer therapy.3. A method for determining the likelihood that a patient with cancer will exhibit benefit from anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a reference level indicates that the patient has increased likelihood of benefit from the anti-cancer therapy.4. A method for optimizing the therapeutic efficacy of an anti-cancer therapy comprising a VEGF-A antagonist , the method comprising:determining an expression level of unmodified VEGF in a sample obtained from the patient, wherein a level of unmodified VEGF in the sample obtained from the patient at or above a ...

SOLID COMPOSITIONS

The present invention features solid compositions comprising a selected HCV inhibitor in an amorphous form. In one embodiment, the selected HCV inhibitor is formulated in an amorphous solid dispersion which comprises a pharmaceutically acceptable hydrophilic polymer and preferably a pharmaceutically acceptable surfactant. 1. A solid composition comprisingan HCV inhibitor selected from telaprevir, BI-201335, TMC-435, vaniprevir, MK-5172, asunaprevir, daclatasvir, danoprevir, setrobuvir, tegobuvir, GS-9451, mericitabine, IDX-184, filibuvir, PSI-7977, PSI-352938, BIT-225, boceprevir, GS-5885 or GS-9256,a pharmaceutically acceptable hydrophilic polymer, andoptionally a pharmaceutically acceptable surfactant.2. The composition of claim 1 , comprising a solid dispersion which includes:said HCV inhibitor andsaid polymer.3. The composition of claim 2 , wherein said polymer has a Tof at least 50° C.4. The composition of claim 3 , further comprising said surfactant.5. The composition of claim 4 , wherein said solid dispersion comprises said surfactant.6. The composition of claim 4 , wherein said polymer is a homopolymer or copolymer of N-vinyl pyrrolidone.7. The composition of claim 4 , wherein said polymer is copovidone.8. The composition of claim 7 , wherein said surfactant is D-alpha-tocopheryl polyethylene glycol 1000 succinate.9. The composition of claim 3 , wherein said solid dispersion is an amorphous solid dispersion.10. The composition of claim 3 , where said solid dispersion is a solid solution.11. The composition of claim 4 , wherein said solid dispersion is an amorphous solid dispersion.12. The composition of claim 4 , where said solid dispersion is a solid solution.13. The composition of claim 1 , further comprising another anti-HCV agent.14. The composition of claim 1 , further comprising an HCV protease inhibitor.15. The composition of claim 1 , further comprising an HCV polymerase inhibitor.16. A process of making the composition of claim 1 , comprising ...

AGENT FOR TREATMENT OF DRY EYE CHARACTERIZED BY COMBINING P2Y2 RECEPTOR AGONIST AND HYALURONIC ACID OR SALT THEREOF, METHOD FOR TREATING DRY EYE, AND USE OF THE P2Y2 RECEPTOR AGONIST AND HYALURONIC ACID OR SALT THEREOF

An agent for treatment of dry eye comprising a combination of a P2Yreceptor agonist at a therapeutically effective concentration and hyaluronic acid or a salt thereof at a therapeutically effective concentration, which agent has a dosage form of an ophthalmic agent, can promote the secretion of tear remarkably and can improve corneal epithelial disorders remarkably, and is therefore expected to be a novel agent for treatment of dry eye. 1. An agent for treatment of dry eye , characterized by comprising a combination of a P2Yreceptor agonist at a therapeutically effective concentration and hyaluronic acid or a salt thereof at a therapeutically effective concentration , wherein the dosage form is an ophthalmic agent.3. The agent for treatment of dry eye according to claim 1 , wherein the P2Yreceptor agonist is P claim 1 ,P-bis(5′-uridyl)tetraphosphate claim 1 , uridine 5′-triphosphate claim 1 , adenosine 5′-triphosphate or a salt thereof.4. The agent for treatment of dry eye according to claim 1 , wherein the ophthalmic agent is an ophthalmic solution or an ophthalmic ointment.5. An ophthalmic solution for treating dry eye claim 1 , characterized by comprising a combination of P claim 1 ,P-bis(5′-uridyl)tetraphosphate or a salt thereof at a concentration of 1 to 5% (w/v) and hyaluronic acid or a salt thereof at a concentration of 0.05 to 0.5% (w/v).6. An ophthalmic solution for treating dry eye claim 1 , characterized by comprising a combination of P claim 1 ,P-bis(5′-uridyl)tetraphosphate or a salt thereof at a concentration of 3% (w/v) and hyaluronic acid or a salt thereof at a concentration of 0.1 to 0.5% (w/v).7. A method for treating dry eye claim 1 , comprising administering a P2Yreceptor agonist at a therapeutically effective concentration and hyaluronic acid or a salt thereof at a therapeutically effective concentration in combination to a patient in need thereof claim 1 , wherein the dosage form is an ophthalmic agent.9. The method for treating dry eye ...

Blood plasma biomarkers for bevacizumab combination therapies for treatment of pancreatic cancer

The present invention provides methods for improving the treatment effect of a chemotherapy regimen of a patient suffering from pancreatic cancer, in particular metastatic pancreatic cancer by adding bevacizumab (Avastin®) to a chemotherapy regimen by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels of patients diagnosed with pancreatic cancer, in particular metastatic pancreatic cancer. In particular, the present invention provides methods of improving the treatment effect, wherein the treatment effect is the overall survival and/or progression-free survival of the patient. The present invention further provides for methods for assessing the sensitivity or responsiveness of a patient to bevacizumab (Avastin®) in combination with a chemotherapy regimen, by determining the expression level, in particular the blood plasma expression level, of one or more of VEGFA, VEGFR2 and PLGF relative to control levels in patients diagnosed with pancreatic cancer, in particular metastatic pancreatic cancer.

Novel IDO Inhibitors and Methods of Use Thereof

Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed. 1. (canceled)3. (canceled)4. (canceled)5. A pharmaceutical composition for the treatment of cancer comprising a pharmaceutically acceptable carrier and an effective amount at least one indoleamine 2 claim 2 ,3-dioxygenase (IDO) inhibitor claim 2 , wherein at least one of said IDO inhibitors is the compound of .616-. (canceled)17. The pharmaceutical composition of claim 5 , further comprising at least one signal transduction inhibitor (STI).18. (canceled)19. (canceled)20. The pharmaceutical composition of claim 5 , further comprising at least one chemotherapeutic agent.21. (canceled)22. (canceled)23. The pharmaceutical composition of claim 20 , wherein said at least one chemotherapeutic agent is selected from the group consisting of paclitaxel (Taxol®) claim 20 , cisplatin claim 20 , docetaxol claim 20 , carboplatin claim 20 , vincristine claim 20 , vinblastine claim 20 , methotrexate claim 20 , cyclophosphamide claim 20 , CPT-11 claim 20 , 5-fluorouracil (5-FU) claim 20 , gemcitabine claim 20 , estramustine claim 20 , carmustine claim 20 , adriamycin (doxorubicin) claim 20 , etoposide claim 20 , arsenic trioxide claim 20 , irinotecan claim 20 , and epothilone derivatives.2434.-. (canceled)35. A compound which is the hydroquinone form of the compound of .36. (canceled)37. The compound of claim 2 , wherein X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , X claim 2 , and Xare H.38. The compound of claim 2 , wherein Xis R.39. The compound of claim 38 , wherein R is aryl.40. The compound of claim 37 , wherein Xis R.41. The compound of claim 39 , wherein R is aryl. This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Patent Application No. 60/918,516, filed on Mar. 16, 2007. The foregoing application is incorporated by reference herein.Pursuant to 35 U.S.C. Section 202(c), it is acknowledged that the United ...

ANTITUMOR COMBINATIONS CONTAINING A VEGF-INHIBITING AGENT AND 5FU OR A DERIVATIVE THEREOF

This invention relates to antitumor combinations comprising a VEGF inhibitor combined with 5-fluorouracil or with a 5-fluoropyrimidine derivative that are therapeutically useful in the treatment of neoplastic diseases, and pharmaceutical compositions comprising such combinations. 1. A pharmaceutical composition comprising a pharmaceutically effective amount of a VEGF inhibitor and a pharmaceutically effective amount of 5-fluorouracil , and a pharmaceutically acceptable excipient.2. A pharmaceutical composition comprising a pharmaceutically effective amount of a VEGF inhibitor and a pharmaceutically effective amount 5-fluoropyrimidine derivative , and a pharmaceutically acceptable excipient.3. A method of treating a neoplastic disease , in a patient in need of such treatment , comprising administering to such patient a pharmaceutically effective amount of a combination of a VEGF inhibitor and 5-fluorouracil ,4. A method of treating a neoplastic disease , in a patient in need of such treatment , comprising administering to such patient a pharmaceutically effective amount of a combination of a VEGF inhibitor and a 5-fluoropyrimidine derivative.5. A pharmaceutical composition according to wherein the 5-fluoropyrimidine derivative is capecitabine or gemcitabine.6. A method according to wherein the 5-fluoropyrimidine derivative is capecitabine or gemcitabine.7. A method according to either of or claim 4 , wherein the VEGF inhibitor is VEGF-Trap.8. A pharmaceutical composition according to either of or wherein the VEGF inhibitor is VEGF-Trap.9. A pharmaceutical composition according to wherein the VEGF inhibitor is VEGF-Trap.10. A method according to wherein the VEGF inhibitor is VEGF-Trap.11. A pharmaceutical composition according to either of or claim 6 , further comprising folinic acid.12. A method according to either of or claim 6 , further comprising administering a pharmaceutically effective amount of folinic acid.13. A method according to wherein the VEGF inhibitor ...

Method of Treating Cancer Using Combination of a Bifunctional Alkylating Agent and DNA Repair Inhibitors

A pharmaceutical composition for treating cancer, in particular drug resistant cancer, comprising an effective amount of bifunctional alkylating agent, an effective amount of a DNA repair inhibitor, and a pharmaceutically acceptable carrier. 1. A pharmaceutical composition for treating cancer comprising an effective amount of bifunctional alkylating agent , an effective amount of a DNA repair inhibitor , and a pharmaceutically acceptable carrier.2. The composition of wherein the bifunctional alkylating agent is a derivative of 3a-aza-cyclopenta[a]indenes.3. The composition of wherein the derivative of 3a-aza-cyclopenta[a]indene is selected from the group consisting of BO-1012 and BO-1509.4. The composition of wherein the DNA repair inhibitor is selected from the group consisting of arsenic trioxide claim 1 , LY294002 claim 1 , and triciribine.5. A method of treating cancer suffered by a mammalian subject comprising administering to the subject an effective amount of bifunctional alkylating agent and an effective amount of a DNA repair inhibitor.6. The method of wherein the subject is administered with the bifunctional alkylating agent before being administered with the DNA repair inhibitor.7. The method of wherein the DNA repair inhibitor is selected from the group consisting of ATO claim 5 , Ly294002 claim 5 , and triciribine.8. The method of wherein the cancer is resistant to an individual therapeutic agent.9. The method of wherein the cancer is human lung cancer.10. The method of wherein the cancer is human bladder cancer.11. The method of wherein the cancer is human breast cancer.12. The method of wherein the cancer is human prostate cancer.13. The method of wherein the cancer is human glioma cancer.14. The method of wherein the cancer is human oral cancer. 1. Field of the InventionThe present application relates to compositions comprising a combination of a bifunctional alkylating agent and DNA repair inhibitors and use of the compositions in treating cancer, ...

COMPOUNDS FOR INHIBITION OF CANCER CELL PROLIFERATION

Methods and small molecule compounds for inhibition of cancer cell proliferation are provided. One example of a class of compounds that may be used is represented by the compound of Formula I or a pharmaceutically acceptable salt, N-oxide or solvate thereof, wherein A, B, D, E, F, G, I, J, R, R, R, R, R, R, R, R, R, R, Rare as described herein. 4. A method for inhibiting cancer cell proliferation claim 1 , the method comprising contacting the cancer cell with a compound of Formula I of .5. The method of claim 1 , wherein the compound of Formula I is in the form of a free base or a pharmaceutically acceptable salt claim 1 , hydrate claim 1 , solvate or N-oxide thereof; and wherein A claim 1 , B claim 1 , D claim 1 , E claim 1 , F claim 1 , G claim 1 , I claim 1 , J claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , R claim 1 , are as described in .6. The method of claim 4 , wherein contact with the cancer cells and the compound of Formula I lasts for a period of time between about 24 hours and about 192 hours or between about 48 hours and about 144 hours.7. The method of claim 4 , wherein the cancer cells comprise colon cancer claim 4 , prostate cancer claim 4 , breast cancer claim 4 , ovarian cancer claim 4 , uterine cancer claim 4 , liver cancer claim 4 , malignant melanoma claim 4 , pancreatic cancer claim 4 , gastric cancer and glioblastoma or other brain cancers.8. The method of claim 4 , further comprising contacting the cancer cells with a cytotoxic or chemotherapeutic anti-cancer drug by co-administration.9. The method of claim 4 , wherein cancer cell proliferation is inhibited.10. The method of claim 4 , further comprising contacting the cancer cells with a sulfonamide that inhibits a Wnt pathway protein or stimulates HIPK2.11. The method of claim 10 , wherein the Wnt pathway protein is TCF4.12. The method of claim 4 , wherein the cancer cells are cancer stem cells.13. The method of claim 4 , ...

Compounds Useful for Inhibiting Chk1

The present invention provides an aminopyrazole compound, or a pharmaceutically acceptable salt thereof, that inhibits Chk1 and is useful in the treatment of cancer. 119.-. (canceled)20. A compound which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazol-3-yl]-l6-(piperidin-3-yloxy)-pyrazin-2-yll-amine , or a pharmaceutically acceptable salt thereof.21. The compound according to which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazo1-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine.22. The compound according to which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazo1-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine methane sulfonic acid salt.23. The compound according to which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazo1-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine acetic acid salt.24. The compound according to which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazo1-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine hemioxalate salt.25. The compound according to which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazo1-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine hemisuccinate salt.26. A pharmaceutical composition comprising a compound which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H -pyrazol-3-yl]-[6-(piperidin-3-yloxy)-pyrazin-2-yl]-amine claim 20 , or a pharmaceutically acceptable salt thereof claim 20 , and a pharmaceutically acceptable carrier claim 20 , diluent claim 20 , or excipient.27. A method of treating cancer wherein the cancer is selected from the group consisting of bladder cancer claim 20 , colon cancer claim 20 , gastric cancer claim 20 , liver cancer claim 20 , lung cancer claim 20 , mammary cancer claim 20 , melanoma claim 20 , ovarian cancer claim 20 , pancreatic cancer claim 20 , mesothelioma claim 20 , renal cancer claim 20 , and uterine cancer claim 20 , comprising administering to a patient in need thereof an effective amount a compound which is (R)-[5-(2-methoxy-6-methyl-pyridin-3-yl)-2H - ...

COMBINATION COMPRISING CNDAC (2'-CYANO-2'-DEOXY-N4-PALMITOYL-1-BETA-D-ARABINOFURANOSYL-CYTOSINE) AND A CYTOTOXIC AGENT

A first aspect of the invention relates to a combination comprising 2′-cyano-2′-deoxy-N-palmitoyl-1-β-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof. A second aspect relates to a pharmaceutical product comprising (i) 2′-cyano-2′-deoxy-N-palmitoyl-1-β-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and (ii) a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof, as a combined preparation for simultaneous, sequential or separate use in therapy. A third aspect relates to a method of treating a proliferative disorder, said method comprising simultaneously, separately or sequentially administering to a subject 2′-cyano-2′-deoxy-N-palmitoyl-1-β-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, and a cytotoxic agent selected from: (a) a HDAC inhibitor; and (b) a topoisomerase inhibitor selected from etoposide, topotecan and SN-38, or a prodrug thereof. A fourth aspect of the invention relates to the use of a subject 2′-cyano-2′-deoxy-N-palmitoyl-1-β-D-arabinofuranosyl-cytosine, or a metabolite thereof, or a pharmaceutically acceptable salt thereof, in the preparation of a medicament for treating cutaneous T-cell lymphoma (CTCL). 1. A combination comprising 2-cyano-2′-deoxy-N-palmitoyl-1-β-D-arabinofuranosyl-cytosine , or a metabolite or pharmaceutically acceptable salt thereof , and a cytotoxic agent , wherein the cytotoxic agent is either selected an HDAC inhibitor or a topoisomerase inhibitor selected from the group consisting of etoposide , topotecan , irinotecan , SN-38 , and a prodrug thereof.28-. (canceled)9. A combination according to wherein the ...

Antitumor T Cell Response Enhancer

An objective of the present invention is to provide novel therapeutic agents for cancer, which have an excellent antitumor effect in cancer patients by enhancing their immune function. The present inventors discovered that the administration of at IL-6 inhibitor and/or gemcitabine or a salt thereof to tumor-bearing organisms yields an excellent antitumor T cell response-enhancing effect, and completed the present invention. In addition, the present inventors discovered that the T cell response-enhancing effect produces an excellent antitumor effect. 1. A composition for enhancing an antitumor T cell response in a tumor-bearing organism , which comprises an interleukin 6 (IL-6) inhibitor and/or gemcitabine or a salt thereof.2. The composition of for enhancing the antitumor T cell response claim 1 , wherein the IL-6 inhibitor and gemcitabine or salt thereof claim 1 , is administered concomitantly.3. The composition of claim 1 , wherein the IL-6 inhibitor is a substance that binds to an IL-6 receptor.4. The composition of claim 3 , wherein the substance that binds to an IL-6 receptor is an anti-IL-6 receptor antibody.5. The composition of claim 4 , wherein the anti-IL-6 receptor antibody is a chimeric claim 4 , humanized claim 4 , or human antibody.6. The composition of claim 1 , wherein the gemcitabine or salt thereof is gemcitabine hydrochloride.7. A method for enhancing an antitumor T cell response claim 1 , which comprises administering an IL-6 inhibitor and/or gemcitabine or a salt thereof to a tumor-bearing organism.8. The method of claim 7 , wherein the IL-6 inhibitor is a substance that binds to an IL-6 receptor.9. The method of claim 8 , wherein the substance that binds to an IL-6 receptor is an anti-IL-6 receptor antibody.10. The method of claim 9 , wherein the anti-IL-6 receptor antibody is a chimeric claim 9 , humanized claim 9 , or human antibody.11. The method of claim 7 , wherein the gemcitabine or salt thereof is gemcitabine hydrochloride.12. An IL-6 ...

METHODS OF TREATING MYELODYSPLASTIC SYNDROMES WITH A COMBINATION THERAPY USING LENALIDOMIDE AND AZACITIDINE

Methods of treating, preventing and/or managing myelodysplastic syndromes are disclosed. Specific methods encompass the administrations of 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidin-2,6-dione in combination with 5-azacytidine. 1. A method of treating a myelodysplastic syndrome , which comprises administering to a patient having a myelodysplastic syndrome a therapeutically effective amount of 5-azacytidine , and a therapeutically effective amount of 3-(4-amino-1-oxo-1 ,3-dihydro-isoindol-2-yl)-piperidine-2 ,6-dione or a pharmaceutically acceptable salt thereof.2. The method of claim 1 , wherein the myelodysplastic syndrome is refractory anemia claim 1 , refractory anemia with ringed sideroblasts claim 1 , refractory anemia with excess blasts claim 1 , refractory anemia with excess blasts in transformation claim 1 , or chronic myelomonocytic leukemia.3. The method of claim 1 , wherein the myelodysplastic syndrome is Intermediate-2 or High risk in international prognostic scoring system (IPSS).4. The method of claim 1 , which further comprises administering to the patient a therapeutically effective amount of at least one additional active agent.5. The method of claim 4 , wherein the additional active agent is capable of improving blood cell production.6. The method of claim 4 , wherein the additional active agent is a cytokine claim 4 , hematopoietic growth factor claim 4 , anti-cancer agent claim 4 , antibiotic claim 4 , proteasome inhibitor claim 4 , or immunosuppressive agent.7. The method of claim 4 , wherein the additional active agent is gemtuzumab ozogamicin claim 4 , etanercept claim 4 , imatinib claim 4 , anti-TNF-α antibodies claim 4 , infliximab claim 4 , G-CSF claim 4 , GM-CSF claim 4 , EPO claim 4 , topotecan claim 4 , pentoxifylline claim 4 , ciprofloxacin claim 4 , irinotecan claim 4 , vinblastine claim 4 , dexamethasone claim 4 , IL2 claim 4 , IL8 claim 4 , IL18 claim 4 , Ara-C claim 4 , vinorelbine claim 4 , isotretinoin claim 4 , 13-cis- ...

Treatment of Cancer Using Hypoxia Activated Prodrugs

Cancer can be treated by administration of a hypoxia-activated prodrug, such as TH-302, alone or in combination with other anticancer agents and/or radiation therapy. In combination therapy, the hypoxia-activated prodrug and another anti-cancer agent or radiation therapy may be administered within the same 24-hour period, and administration of the hypoxia-activated prodrug may be completed prior to beginning administration of the other anticancer agent or radiation therapy. 1. A method of treating cancer comprising administering TH-302 and a therapeutically effective dose of an anticancer drug that is not a hypoxia activated prodrug to a patient in need of cancer therapy ,{'sup': 2', '2, 'wherein TH-302 is administered intravenously in an amount in the range of 200 mg/mto 500 mg/mand administration of the anticancer drug that is not a hypoxia activated prodrug begins 30 minutes to 8 hours after administration of TH-302 is completed.'}2. The method of claim 1 , wherein the drug that is not a hypoxia activated prodrug is administered 2 hours to 6 hours after administration of TH-302 is complete.3. The method of claim 1 , wherein the anticancer drug that is not a hypoxia activated prodrug is docetaxel claim 1 , pemetrexed claim 1 , doxorubicin claim 1 , gemcitabine claim 1 , cisplatin claim 1 , carboplatin or 5-fluorouracil.4. The method of wherein the patient is in need of treatment for lung cancer and the anticancer drug that is not a hypoxia activated prodrug is docetaxel claim 3 , paclitaxel claim 3 , pemetrexed claim 3 , doxorubicin claim 3 , gemcitabine claim 3 , 5-fluorouracil claim 3 , cisplatin claim 3 , or carboplatin.5. The method of wherein the patient is in need of treatment for prostate cancer and the anticancer drug that is not a hypoxia activated prodrug is docetaxel.6. The method of wherein the patient is in need of treatment for pancreatic cancer and the anticancer drug that is not a hypoxia activated prodrug is gemcitabine.7. The method of wherein ...

STABILIZED CHLORITE SOLUTIONS IN COMBINATION WITH FLUROPYRIMIDINES FOR CANCER

Pharmaceutical compositions for treating neoplastic disorders and uses thereof are provided. Said pharmaceutical compositions comprise stabilized chlorite solutions (e.g. WFIO) and a fluoropyrimidine, 5-FU, or a 5-FU prodrug (e.g. capecitabine, doxifluridine, UFT, S-1, or BOF-A2). The use of the above stabilized chlorite solution in combination with a fluoropyrimidine dramatically improves the quality of life index (QOL) of a patient undergoing cancer chemotherapy. Cancers that can be treated include cancers of the pancreas, gastrointestinal, head, neck, and breast. 1. A method of treating a neoplastic disorder in a patient , comprising administering to the patient an effective amount of a combination of a cytotoxic agent and a stabilized chlorite solution , wherein the cytotoxic agent comprises 5-fluorouracil (5-FU) or a compound that is converted to 5-FU in the body of the patient , wherein the neoplastic disorder is a tumor of the gastrointestinal tract , head , neck , breast or pancreas.25.-. (canceled)6. The method according to claim 1 , wherein the neoplastic disorder is a tumor of the pancreas.7. The method according to claim 1 , wherein the cytotoxic agent comprises 5-FU.8. The method according to claim 1 , wherein the cytotoxic agent comprises a compound that is converted to 5-FU in the body of the patient.11. The method according to claim 1 , wherein the cytotoxic agent comprises capecitabine.12. The method according to claim 1 , wherein the stabilized chlorite solution comprises WF10.14. The method according to claim 13 , wherein the enzyme is dihydropyrimidine dehydrogenase.15. The method according to claim 13 , wherein the cytotoxic agent is 5-fluorouracil (5-FU) or a compound that is metabolized to 5-FU in vivo.16. (canceled)18. A pharmaceutical composition comprising a cytotoxic agent and a stabilized chlorite solution claim 13 , wherein the cytotoxic agent comprises 5-fluorouracil (5-FU) or a compound that is converted in vivo to 5-FU.19. The ...

GLYCOSIDE DERIVATIVES AND USES THEREOF

The present invention provides a compound of formula I; 63. The compound of anyone of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein n is 0.736. The compound of anyone of - and claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein q is 0.8. The compound of anyone of the preceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein V is —OR.9. The compound of anyone of the preceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein R claims 1 , R claims 1 , and Rare hydrogen.10. The compound of anyone of the preceding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris halo claims 1 , Calkyl claims 1 , or Ccycloalkyl.11. The compound of anyone of the preceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris bromo claims 1 , ethyl or cyclopropyl.12. The compound of anyone of the preceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris ethyl.13. The compound of anyone of the proceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein X is O.1412. The compound of anyone of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein X is S.1512. The compound of anyone of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein X is S(O).1612. The compound of anyone of - claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein X is NR.17. The compound of anyone of the proceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris Calkyl claims 1 , haloCalkyl claims 1 , Ccycloalkyl claims 1 , phenyl claims 1 , or a 5- to 6-membered heteroaryl.18. The compound of anyone of the proceeding claims claims 1 , or a pharmaceutically acceptable salt thereof claims 1 , wherein Ris methyl.19. The compound of claim 16 , or a ...

TREATMENT WITH ANTI-ErbB2 ANTIBODIES

The present invention concerns the treatment of disorders characterized by the overexpression of ErbB2. More specifically, the invention concerns the treatment of human patients susceptible to or diagnosed with cancer overexpressing ErbB2 with a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline, e.g. doxorubicin or epirubicin. The invention further provides a method of treating cancer in a human patient comprising administering effective amounts of an anti-ErbB2 antibody and a cardioprotectant to the patient. 1. A method for the treatment of a human patient susceptible to or diagnosed with a disorder characterized by overexpression of ErbB2 receptor , comprising administering an effective amount of a combination of an anti-ErbB2 antibody and a chemotherapeutic agent other than an anthracycline derivative , in the absence of an anthracycline derivative , to the human patient.2. The method of wherein the chemotherapeutic agent is capecitabine.3. A method for the treatment of a human patient with breast cancer characterized by overexpression of ErbB2 receptor claim 1 , comprising administering a combination of an anti-ErbB2 antibody and capecitabine claim 1 , in the absence of an anthracycline derivative claim 1 , to the human patient in an amount effective to treat the cancer claim 1 , wherein the treatment increases time to disease progression compared to therapy with capecitabine alone claim 1 , and wherein said antibody binds to epitope 4D5 within the ErbB2 extracellular domain sequence.4. The method of wherein said breast cancer is metastatic breast carcinoma.5. The method of wherein said antibody is a humanized 4D5 anti-ErbB2 antibody.6. The method of wherein efficacy is measured by determining time to disease progression or response rate.7. The method of wherein the antibody is not conjugated with the capecitabine.8. A method for the treatment of a human patient with an ErbB2-expressing breast cancer claim 3 , ...

COMBINATIONS AND MODES OF ADMINISTRATION OF THERAPEUTIC AGENTS AND COMBINATION THERAPY

The present invention provides combination therapy methods of treating proliferative diseases (such as cancer) comprising a first therapy comprising administering to an individual an effective amount of a taxane in a nanoparticle composition, and a second therapy which may include, for example, radiation, surgery, administration of chemotherapeutic agents, or combinations thereof. Also provided are methods of administering to an individual a drug taxane in a nanoparticle composition based on a metronomic dosing regime. 1. A method of treating a proliferative disease in an individual comprising administering to the individual:a) an effective amount of a composition comprising nanoparticles comprising a taxane and an albumin, andb) an effective amount of at least one other chemotherapeutic agent, wherein said chemotherapeutic agent is selected from the group consisting of antimetabolites, platinum-based agents, alkylating agents, tyrosine kinase inhibitors, anthracycline antibiotics, vinca alkloids, proteasome inhibitors, macrolides, and topoisomerase inhibitors.2. The method according to claim 1 , wherein said chemotherapeutic agent is an antimetabolite agent.3. The method according to claim 2 , wherein said chemotherapeutic agent is a platinum-based agent.4. The method according to claim 1 , wherein said chemotherapeutic agent is a tyrosine kinase inhibitor.5. The method according to claim 1 , wherein the proliferative disease is cancer.6. The method according to claim 1 , wherein the taxane is paclitaxel.7. The method according to claim 6 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.8. The method according to claim 1 , wherein the average diameter of the nanoparticles in the composition is no greater than about 200 nm.9. The method according to claim 1 , wherein the individual is a human.10. A method of treating a tumor in an individual comprising:a) a first therapy comprising administering to the individual ...

Combinatory Cancer Treatment

The present invention relates to a pharmaceutical composition for treating a neoplasm, a preneoplasm, a proliferative disorder and/or a precancerous lesion, the use of such compositions for the treatment of the listed conditions, and methods of treating the listed conditions. The composition of the present invention comprises an inhibitor of eIF4E, a methltransferase inhibitor, and a pharmaceutically acceptable carrier. 1. A pharmaceutical composition suitable for treating a pre-neoplasm , precancerous lesion , neoplasm or a proliferative disorder , wherein the composition comprises an inhibitor of eIF4E , a methyltransferase inhibitor , and a pharmaceutically acceptable carrier.2. The pharmaceutical composition according to claim 1 , wherein the inhibitor of eIF4E is ribavirin.3. The pharmaceutical composition according to claim 2 , wherein the methyltransferase inhibitor is azacytidine or decitabine.4. The pharmaceutical composition according to claim 3 , wherein the inhibitor of eIF4E and methyltransferase inhibitor are present in a ratio ranging from about 1:5 to about 5:1.5. The pharmaceutical composition according to claim 4 , wherein the inhibitor of eIF4E and methyltransferase inhibitor are present in a ratio ranging from about 1:3 to about 3:1.6. The pharmaceutical composition according to claim 1 , wherein the inhibitor of eIF4E and methyltransferase inhibitor are sequentially or simultaneously co-administered.7. The pharmaceutical composition according to claim 1 , wherein the pre-neoplasm or precancerous lesion is any of the family of proliferative disorders that lead to the development of solid or hematological neoplasms.8. (canceled)9. (canceled)10. (canceled)11. (canceled)12. The pharmaceutical composition according to claim 1 , wherein the neoplasm is a cancer.13. The pharmaceutical composition according to claim 12 , wherein said cancer is selected from the group consisting of: leukemia claim 12 , acute myeloid leukemia claim 12 , acute myelocytic ...

Compounds and Compositions for the Treatment of Cancer

New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of a combination of two of these compounds is described and the use of the combination of one of these compounds with an anticancer agent such as decarbazine, doxorubicin, daunorubicin, cyclophosphamide, busulfex, busulfan, vinblastine, vincristine, bleomycin, etoposide, topotecan, irinotecan, taxotere, taxol, 5-fluorouracil, methotrexate, gemcitabine, cisplatin, carboplatin and chlorambucil. 130-. (canceled)37. The method of claim 31 , wherein the pharmaceutically acceptable salt is a base addition salt.38. The method of claim 37 , wherein the base addition salt comprises a metal counterion selected from sodium claim 37 , potassium claim 37 , magnesium claim 37 , calcium and lithium.39. The method of claim 38 , wherein the metal counterion is sodium.41. The method of claim 40 , wherein the compound is Compound I claim 40 , II claim 40 , VIII claim 40 , XIII claim 40 , XV claim 40 , XVII claim 40 , XVIII claim 40 , XIX or XX.42. The method of claim 40 , wherein the compound is Compound I claim 40 , II claim 40 , XV claim 40 , XVII or XIX.43. The method of claim 31 , wherein said subject is a human patient.44. The method of claim 31 , wherein the cancer is bladder cancer claim 31 , breast cancer claim 31 , colorectal cancer claim 31 , kidney cancer claim 31 , melanoma claim 31 , non-Hodgkin's lymphoma claim 31 , leukemia claim 31 , ovarian cancer claim 31 , pancreatic cancer claim 31 , prostate cancer or uterine cancer.45. The method of claim 31 , wherein the cancer is breast cancer claim 31 , colorectal cancer claim 31 , leukemia cancer claim 31 , melanoma cancer or pancreatic cancer.46. The method of claim 31 , wherein the compound is used in combination with an anticancer agent.47. The method of claim 46 , wherein ...

METHODS FOR TREATING CANCER USING TOR KINASE INHIBITOR COMBINATION THERAPY

Provided herein are methods for treating or preventing advanced non-small cell lung cancer, comprising administering an effective amount of a TOR kinase inhibitor and an effective amount of erlotinib or a cytidine analog to a patient having advanced non-small cell lung cancer. 1. A method for treating advanced non-small cell lung cancer , comprising administering an effective amount of a TOR kinase inhibitor in combination with an effective amount of erlotinib or a cytidine analog to a patient having advanced non-small cell lung cancer.2. The method of claim 1 , comprising administration of a TOR kinase inhibitor in combination with an effective amount of erlotinib to a patient having advanced non-small cell lung cancer.3. The method of claim 1 , comprising administration of a TOR kinase inhibitor in combination with an effective amount of a cytidine analog to a patient having advanced non-small cell lung cancer.4. The method of claim 3 , wherein the cytidine analog is azacitidine.5. The method of claim 4 , wherein the azacitidine is oral azacitidine.6. A method for achieving a Response Evaluation Criteria in Solid Tumors (RECIST 1.1) of complete response claim 4 , partial response or stable disease in a patient having advanced non-small cell lung cancer claim 4 , comprising administering an effective amount of a TOR kinase inhibitor in combination with an effective amount of erlotinib or a cytidine analog to said patient.7. The method of claim 6 , comprising administration of a TOR kinase inhibitor in combination with an effective amount of erlotinib to a patient having advanced non-small cell lung cancer.8. The method of claim 6 , comprising administration of a TOR kinase inhibitor in combination with an effective amount of a cytidine analog to a patient having advanced non-small cell lung cancer.9. The method of claim 8 , wherein the cytidine analog is azacitidine.10. The method of claim 9 , wherein the azacitidine is oral azacitidine.11. A method for increasing ...

Methods for Treating Patients Undergoing Multi-Cycle Chemotherapy

The present invention provides methods for treating a patient undergoing multi-cycle chemotherapy that provides significantly improved platelet counts in the patients, and facilitates retention of dose intensity from cycle to cycle of the chemotherapy. 1. A method for treating a patient undergoing multi-cycle chemotherapy , comprising(a) administering a first cycle of chemotherapy to the patient;(b) administering an amount effective of a hematopoietic growth factor, or a pharmaceutical salt thereof, to increase platelet counts and/or to facilitate retention of dose-intensity, wherein the peptide is administered between 18-48 hours after ending the first cycle of chemotherapy; and(c) administering a second cycle of the chemotherapy to the patient, wherein the second cycle of the chemotherapy is initiated 18-48 hours after step (b); and(d) repeating steps (b) and (c) a suitable number of times to treat the patient.2. The method of claim 1 , wherein the hematopoietic growth factor is selected from the group consisting of angiotensin and angiotensin analogues claim 1 , granulocyte colony stimulating factor (G-CSF) claim 1 , granulocyte-macrophage-CSF (GM-CSF) claim 1 , epidermal growth factor (EGF) claim 1 , interleukin 11 claim 1 , erythropoietin claim 1 , thrombopoietin claim 1 , megakaryocyte development and growth factor claim 1 , pixykines claim 1 , stem cell factor claim 1 , FLT-ligand claim 1 , and interleukins 1 claim 1 , 3 claim 1 , 6 claim 1 , and 73. The method of claim 1 , wherein the hematopoietic growth factor is a peptide comprising at least 5 contiguous amino acids of Asp-Arg-Val-Tyr-Ile-His-Pro (SEQ ID NO:1).4. The method of claim 3 , wherein the peptide comprises the amino acid sequence of SEQ ID NO:1.5. The method of claim 1 , wherein the chemotherapy comprises nucleoside analog therapy.6. The method of claim 5 , wherein the nucleoside analog comprises gemcitabine.7. The method of claim 1 , wherein the chemotherapy comprises platin therapy.8. The ...

Cellular blood markers for early diagnosis of als and for als progression

The present invention provides methods for early diagnosis of amyotrophic lateral sclerosis (ALS) and for determining the efficacy of a treatment for ALS in an ALS patient, i.e., monitoring ALS progression, utilizing cellular blood markers; as well as kits for carrying out these methods.

Modified drugs for use in liposomal nanoparticles

Drug derivatives are provided herein which are suitable for loading into liposomal nanoparticle carriers. In some preferred aspects, the derivatives comprise a poorly water-soluble drug derivatized with a weak-base moiety that facilitates active loading of the drug through a LN transmembrane pH or ion gradient into the aqueous interior of the LN. The weak-base moiety can optionally comprise a lipophilic domain that facilitates active loading of the drug to the inner monolayer of the liposomal membrane. Advantageously, LN formulations of the drug derivatives exhibit improved solubility, reduced toxicity, enhanced efficacy, and/or other benefits relative to the corresponding free drugs.

ANTI-BACTERIAL ACTIVITY OF 9-HYDROXY DERIVATIVES OF 6,11-BICYCLOLIDES

The present invention discloses compounds of formula (I) or pharmaceutically acceptable salts, esters, or prodrugs thereof: 8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of or a pharmaceutically acceptable salt claim 1 , ester or prodrug thereof claim 1 , in combination with a pharmaceutically acceptable carrier.9. A method for treating a bacterial infection in a subject claim 8 , comprising administering to said subject a therapeutically effective amount of a pharmaceutical composition according to .10. A method of treating cystic fibrosis in subject claim 8 , comprising administering to said subject claim 8 , a therapeutically effective amount of a pharmaceutical composition of .11. A method of treating inflammation in a subject comprising administering to said subject claim 8 , therapeutically effective amount of a pharmaceutical composition of . This application is a continuation of U.S. application Ser. No. 12/437,616, filed May 8, 2009, which claims the benefit of U.S. Provisional Application No. 61/051,991, filed on May 9, 2008. The entire teachings of the above applications are incorporated herein by reference.The present invention relates to novel semisynthetic macrolides having antibacterial activity that are useful in the treatment and prevention of bacterial infections. More particularly, the invention relates to spC9 oxygenated compounds, compositions containing such compounds and methods for using the same, as well as processes for making such compounds.The spectrum of activity of macrolides, including erythromycin, covers most relevant bacterial species responsible for upper and lower respiratory tract infections. 14-membered ring macrolides are well known for their overall efficacy, safety and lack of serious side effects. Erythromycin, however, is quickly degraded into inactive products in the acidic medium of the stomach resulting in low bioavailability and gastrointestinal side effects. Improvement of ...

COMBINATION OF CHECKPOINT KINASE I INHIBITORS AND WEE I KINASE INHIBITORS

A combination of a CHK1 inhibitor and a WEE1 inhibitor are provided. 1. A use of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors in combination with a WEE1 inhibitor.2. A use of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors in combination with a WEE1 inhibitor to treat cancer.3. A use of a pharmaceutical composition comprising a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors in combination with a pharmaceutical composition comprising a WEE1 inhibitor to treat a hyperproliferative disease , such as cancer.4. A use of a pharmaceutical composition comprising an effective amount of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors in combination with a pharmaceutical composition comprising an effective amount of a WEE1 inhibitor to treat cancer.5. A use of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors for the manufacture of a medicament for the combined use with a WEE1 inhibitor in the treatment of a hyperproliferative disease , such as cancer.6. A pharmaceutical composition comprising a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors and a WEE1 inhibitor.7. A pharmaceutical composition comprising an effective amount of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors and an effective amount of a WEE1 inhibitor.8. A pharmaceutical composition for the treatment or prevention of cancer , comprising a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors and a WEE1 inhibitor.9. A pharmaceutical composition for the treatment or prevention of cancer , comprising an effective amount of a CHK1 inhibitor selected from the group consisting of the '926 CHK1 Inhibitors and an effective amount of a WEE1 inhibitor.10. A method for treating or preventing cancer by administering a CHK1 inhibitor selected from the group consisting of the '926 ...

Novel antibacterial compounds, methods of making them, and uses thereof

The present invention relates to novel therapeutics with antibacterial activity, processes for their preparation, and pharmaceutical, veterinary and nutritional compositions containing them as active ingredients. The present invention also relates to uses of the novel therapeutics, for example, as medicants or food additives in the treatment of bacterial infections or to aid body mass gain in a subject.

BONE-TARGETING BISPHOSPHONATE DUPLEX DRUGS

The present invention relates to novel bisphosphonate duplex drugs, methods for preparing said compound; pharmaceutical compositions containing the same; as well as the use of said compounds in human and veterinary medicine, and, in particular, for treating tumors, viral infections; or dental disorders. 3. The compound of claim 2 , whereinresidues A independently of each other represent a proton, or a alkali metal cation;Y represents O;n represents an integer of 2 or 3;{'sup': '1', 'Rrepresents hydrogen, halogen, azido or hydroxy;'}{'sup': '2', 'Rrepresents hydrogen or hydroxy;'}{'sup': '3', 'Rrepresents hydrogen or hydroxy;'}{'sup': '4', 'Rrepresents hydrogen, halogen, or linear or branched alkyl;'}{'sup': '5', 'Rrepresents hydrogen or lower alkinyl; and'}{'sup': '6', 'Rrepresents hydroxy or acyl.'}4. The compound of claim 2 , wherein{'sup': +', '+, 'residues A independently of each other represent Na or K;'}Y represents O;n represents an integer of 2 or 3;{'sup': '1', 'Rrepresents azido or hydroxy;'}{'sup': '2', 'Rrepresents hydrogen or hydroxy;'}{'sup': '3', 'Rrepresents hydrogen or hydroxy;'}{'sup': '4', 'Rrepresents hydrogen, fluoro or methyl;'}{'sup': '5', 'Rrepresents hydrogen; and'}{'sup': '6', 'Rrepresents hydroxy.'}5. (canceled)6. A method for the treatment of tumours or viral infections in a mammal claim 1 , comprising administering the compound of to the mammal.7. A method for the treatment of bone tumours in a mammal claim 1 , comprising administering the compound of to the mammal.8. A pharmaceutical composition comprising in a pharmaceutically acceptable carrier at least one compound of .11. The method of claim 10 , wherein the aminophosphonate compound is selected from alendronate and pamidronate.12. The method of claim 7 , wherein the bone tumours are metastatic bone tumours.13. The method of claim 6 , wherein the mammal is a human.14. The method of claim 7 , wherein the mammal is a human.15. The composition of claim 8 , wherein the composition ...

Cdk-inhibiting pyrrolopyrimidinone carboxamide derivative or pharmaceutically acceptable salt thereof, and pharmaceutical composition containing the same as active ingredient for preventing or treating hepatocellular carcinoma

The present invention relates to a CDK-inhibiting pyrrolopyrimidinone carboxamide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition containing same as an active ingredient for preventing or treating liver cell cancer, and the composition containing the pyrrolopyrimidinone carboxamide derivative of the present invention suppresses the cell growth of SNU-354 cell, which is a liver cancer stem cell in humans, by inhibiting CDK1 and CDK2, and induces cell apoptosis of the cell by inhibiting CDK7 and CDK 7, and thus can be effective in use for preventing or treating liver cell cancer.