Compositions and methods for the diagnosis and treatment of kidney disease

Polymorphisms associated with the CD2AP protein are disclosed. Compositions and methods for the diagnosis and treatment of kidney disease are also disclosed.

Treatment of gout

Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions.

TREATMENT OF GOUT AND HYPERURICEMIA

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 6 mg/dL.2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. The method of claim 1 , wherein the gout in the human is characterized by the presence of large accumulated deposits of uric acid or tophi.7. (canceled)8. (canceled)9. (canceled)10. The method of claim 1 , wherein the daily dose of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is about 400 mg.11. The method of claim 1 , wherein the daily dose of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is about 200 mg.12. The method of claim 1 , wherein the daily dose is administered orally.13. The method of claim 1 , wherein the daily dose is administered in the morning.14. The method of claim 1 , wherein the daily dose is administered with food.15. A method of reducing serum uric acid levels claim 1 , treating hyperuricemia claim 1 , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and allopurinol to the human claim 1 , wherein said method providesserum urate levels of less than 6 mg/dL.16. (canceled)17. (canceled)18. (canceled)19. ...

Treatment of Gout and Hyperuricemia

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.2. A method of reducing serum uric acid levels in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.3. A method of treating hyperuricemia in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to a subject , wherein said method provides:a. serum urate levels of less than 6 mg/dL;b. serum urate levels of less than 5 mg/dL;c. serum urate levels of less than 4 mg/dL;d. serum urate levels of less than 3 mg/dL;e. serum urate levels intraday change of more than 50%;f. serum urate levels intraday change of more than 60%;g. or a combination thereof.4. A method of treating ...

TREATMENT OF GOUT

Sodium 2-(5-bromo-4-(4-cyclopropyl-naphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and colchicine to a subject.2. The method of claim 1 , wherein said method provides greater mean gout flare reduction than co-administration of colchicine and a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.3. The method of claim 1 , wherein the total dosage of colchicine administered during co-administration with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least 50% less than the total dosage of colchicine that would be required for a similar effect when co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.4. The method of claim 1 , wherein the amount of time that colchicine is co-administered with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least one week less than would be required for a similar effect when colchicine is co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.5. A method of reducing monosodium urate induced inflammation in a subject in need thereof claim 1 , the method comprising administering a pharmaceutical composition comprising a pharmaceutical agent having both uricosuric and anti-inflammatory activity.6. The method of claim 5 , wherein the pharmaceutical agent is a URAT1 inhibitor with anti-inflammatory activity.7. The method of claim 5 , wherein the pharmaceutical ...

CXCR-2 inhibitors for treating crystal arthropathy disorders

N-(2-((2,3-difluorobenzyl)thio)-6-(((2R,3S)-3,4-dihydroxybutan-2-yl)oxy)pyrimidin-4-yl)azetidine-1-sulfonamide (compound 3) and N-(6-(((2R,3S)-3,4-dihydroxy butan-2-yl)oxy)-2-((4-fluorobenzyl)thio)pyrimidin-4-yl)-3-methyl-azetidine-1-sulfonamide (compound 4) are known chemokine modulators and are therefore useful in the treatment of diseases/conditions in which modulation of chemokine receptor activity is beneficial. In particular, provided herein are compositions and methods for the treatment and prevention of gout.

HYPERTENSION AND HYPERURICEMIA

A method for treating hypertension in a subject in need thereof (e.g., wherein said treatment does not result in an increase in serum uric acid levels, abnormally elevated serum uric acid levels, hyperuricemia, serum uric acid levels of above 6 mg/dL, or in the development of gout in the subject), the method comprising administering to the subject: a. a thiazide diuretic; and b. an organic anion transporter 4 (OAT4) inhibitor. The thiazide diuretic is selected from hydrochlorothiazide, bendroflumethiazide, benzothiadiazine, hydroflumethiazide, clorothiazide, methyclothiazide, polythiazide, chlorthalidone, metolazone, indapamide, bumetanide, ethacrynic acid, furosemide or torsemide. The OAT4 inhibitor is 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid or a pharmaceutically acceptable salt thereof. 115-. (canceled)16. A method for treating gout in a patient on concomitant thiazide diuretics , wherein the patient is not adequately responding to a non-lesinurad urate lowering therapy , the method comprising further administering to the patient an effective amount of lesinurad.17. The method of claim 16 , wherein 200 mg of lesinurad is administered.18. The method of claim 16 , wherein 400 mg of lesinurad is administered.19. The method of claim 16 , wherein the non-lesinurad urate lowering therapy is allopurinol.20. A method for reducing the incidences of or likelihood of or reversing hyperuricemia or gout in a patient receiving thiazide treatment claim 16 , comprising administering an OAT4 inhibitor to the patient.21. The method of claim 20 , wherein the OAT4 inhibitor is 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 20 ,2 claim 20 ,4-triazol-3-ylthio)acetic acid or a pharmaceutically acceptable salt thereof.22. The method of claim 20 , wherein the thiazide treatment is treatment with hydrochlorothiazide claim 20 , bendroflumethiazide claim 20 , benzothiadiazine claim 20 , hydroflumethiazide claim 20 , chlorothiazide claim 20 , ...

Treatment of gout and hyperuricemia

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described.

Compositions and methods for the diagnosis and treatment of kidney disease

Polymorphisms associated with the CD2AP protein are disclosed. Compositions and methods for the diagnosis and treatment of kidney disease are also disclosed.

Combinations of mek inhibitors and raf kinase inhibitors and uses thereof

This invention concerns combinations of inhibitors of MEK, Raf protein kinases, and other kinases including VEGFR1-3 and PDGFR-β. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer and other hyperproliferative disorders.

TREATMENT OF GOUT AND HYPERURICEMIA

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described. 1. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 6 mg/dL; andwherein said method provides a serum urate levels intraday change from baseline of more than 50%.2. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method providesserum urate levels of less than 4 mg/dL.3. (canceled)4. (canceled)5. (canceled)6. A method of treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein said method provides serum urate levels of less than 6 mg/dL; and wherein the gout in the human is characterized by the presence of large accumulated deposits of uric acid or tophi.725.-. (canceled)26. A method of reducing serum uric acid levels , treating hyperuricemia , or treating gout in a human comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and febuxostat to the human , wherein the method provides serum urate levels of less than 6 mg/dL , and wherein said method results in an adverse event in less than 15% of the subjects. This ...

COMPOSITIONS AND METHODS FOR THE DIAGNOSIS AND TREATMENT OF DISEASES OF THE LIVER

Provided herein are novel molecular markers and targets of liver disease, including NAFLD, NASH, liver fibrosis and related conditions. Also provided herein are methods of screening for modulators of such molecular markers and targets for the treatment of diseases of the liver as well as the modulators useful for treating such disease. Also provided are novel molecular markers useful for diagnosing diseases of the liver, including, NAFLD, NASH, liver fibrosis and related conditions, and for monitoring the progression and treatment of such disease of the liver. 1. A molecular marker of liver disease , said molecular marker being selected from the group consisting of at least one of LOXL4 , CHRM2 , DMKN , QPRT , and SLC12A8.2. The molecular marker of further comprising a molecular target useful for screening for modulators of liver disease in a patient wherein said molecular target is selected from the group consisting of at least one of LOXL4 claim 1 , CHRM2 claim 1 , DMKN claim 1 , QPRT and SLC12A8.3. The molecular marker of further comprising a molecular target capable of treating liver disease in a patient when contacted by a modulator claim 1 , said molecular target being selected from the group consisting of at least one of LOXL4 claim 1 , CHRM2 claim 1 , DMKN claim 1 , QPRT claim 1 , and SLC12A8.4. The molecular marker of wherein the molecular target is QPRT.5. The molecular marker of wherein the molecular target is QPRT.6. The molecular marker of wherein the expression level of the molecular marker is greater in a patient with liver disease. The molecular marker of wherein the liver disease in said patient is selected from the group consisting of non-alcoholic fatty liver disease claim 3 , nonalcoholic steatohepatitis claim 3 , fibrosis of the liver and combinations thereof.8. A method of identifying modulators for treating diseases of the liver in a patient claim 3 , the method comprising:a. Providing one or more molecular targets associated with liver ...

Cxcr-2 inhibitors for treating crystal arthropathy disorders

N-(2-((2,3-difluorobenzyl)thio)-6-(((2R,3S)-3,4-dihydroxybutan-2-yl)oxy)pyrimidin-4-yl)azetidine-1-sulfonamide (compound 3) and N-(6-(((2R,3S)-3,4-dihydroxy butan-2-yl)oxy)-2-((4-fluoro benzyl)thio)pyrimidin-4-yl)-3-methyl-azetidine-1-sulfonamide (compound 4) are known chemokine modulators and are therefore useful in the treatment of diseases/conditions in which modulation of chemokine receptor activity is beneficial. In particular, provided herein are compositions and methods for the treatment and prevention of gout.

COMPOSITIONS AND METHODS FOR THE DIAGNOSIS AND TREATMENT OF DISEASES OF THE LIVER

Provided herein are novel molecular markers and targets of liver disease, including NAFLD, NASH, liver fibrosis and related conditions. Also provided herein are methods of screening for modulators of such molecular markers and targets for the treatment of diseases of the liver as well as the modulators useful for treating such disease. Also provided are novel molecular markers useful for diagnosing diseases of the liver, including, NAFLD, NASH, liver fibrosis and related conditions, and for monitoring the progression and treatment of such disease of the liver. 1. A molecular marker of liver disease , said molecular marker being selected from the group consisting of at least one of CCRL2 , GALNT6 , MARC1 and SLC1A1.2. The molecular marker of further comprising a molecular target useful for screening for modulators of liver disease in a patient wherein said molecular target is selected from the group consisting of at least one of CCRL2 claim 1 , GALNT6 claim 1 , MARC1 and SLC1A1.3. The molecular marker of further comprising a molecular target capable of treating liver disease in a patient when contacted by a modulator claim 1 , said molecular target being selected from the group consisting of at least one of CCRL2 claim 1 , GALNT6 claim 1 , MARC1 and SLC1A1.4. The molecular marker of wherein the molecular target is GALNT6.5. The molecular marker of wherein the molecular target is GALNT6.6. The molecular marker of wherein the expression level of the molecular marker is greater in a patient with liver disease.7. The molecular marker of wherein the liver disease in said patient is selected from the group consisting of non-alcoholic fatty liver disease claim 6 , nonalcoholic steatohepatitis claim 6 , fibrosis of the liver and combinations thereof.8. A method of identifying modulators for treating diseases of the liver in a patient claim 6 , the method comprising:a. Providing one or more molecular targets associated with liver disease;b. Contacting the one or more ...

COMBINATIONS OF MEK INHIBITORS AND RAF KINASE INHIBITORS AND USES THEREOF

This invention concerns combinations of inhibitors of MEK, Raf protein kinases, and other kinases including VEGFR1-3 and PDGFR-β. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer and other hyperproliferative disorders. 1. (canceled)3. (canceled)4. The method of claim 2 , wherein the administration of the combination of the MEK protein kinase inhibitor and the Raf protein kinase inhibitor to a first patient provides an increase in apoptosis level at about day 7 compared to the combined apoptosis level by administration of either inhibitor alone.5. The method of wherein the administration of the combination of the MEK protein kinase inhibitor and the Raf protein kinase inhibitor to the first patient provides an increase in apoptosis level at about day 7 compared to the combined apoptosis level at about day 7 of (1) a second patient administered only the MEK protein kinase inhibitor and (2) a third patient administered only the Raf protein kinase inhibitor.6. The method of wherein the apoptosis levels are measured with an in vivo apoptosis assay.7. The pharmaceutical combinationmethod of wherein the increased apoptosis level of the first patient at about day 7 is greater than about a 50% increase in apoptosis.8. The method of wherein the increased apoptosis level of the first patient at about day 7 is about a 50% to about a 500% increase in apoptosis.9. The method of wherein the increased apoptosis level of the first patient at about day 7 is about a 100% to about a 500% increase in apoptosis.10. The method of wherein the increased apoptosis level of the first patient at about day 7 is about a 200% to about a 500% increase in apoptosis.11. (canceled)12. The method of claim 2 , wherein contacting a first sample of cancer cells with the combination of the MEK protein kinase inhibitor and ...

SYSTEMS AND METHODS FOR AUTOMATED PRESCRIPTION DISPENSING

The presently described systems and methods for automated prescription dispensing provide a virtual prescription verification environment that enables a pharmacist to fill prescriptions, control and remotely verify the performance of pharmacy robotic devices, and counsel patients effectively through a highly secure application. 1. A system for automated prescription dispensing , comprising:a robotic device configured to fill and dispense prescriptions;an application that when executed provides a virtual prescription verification environment;at least one imaging device situated to observe the robotic device filling a prescription; and receives a first input for a prescription for a patient;', 'transmits instructions to the robotic device to fill the prescription based on the first input;', 'receives visual data from the at least one imaging device of the robotic device filling the prescription;', 'displays the visual data;', 'receives an input verification status of a prescription based on the visual data; and', 'transmits an action instruction instructing the robotic device to perform an action associated with the filled prescription based on the verification status., 'a computing device equipped with a processor and configured to execute the application providing the virtual prescription verification environment, the computing device communicatively coupled to the robotic device and the imaging device, the virtual prescription verification environment when executed2. The system of claim 1 , wherein the input verification status is valid and the action is dispensing the filled prescription.3. The system of claim 1 , wherein the input verification status is invalid and the action is an instruction to the robotic device to refrain from dispensing the filled prescription or reject the filled prescription.4. The system of claim 1 , further comprising:a database including prescription information for a plurality of prescriptions, wherein the virtual prescription ...

TREATMENT OF GOUT

Sodium 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio) acetate is described. In addition, pharmaceutical compositions and uses such compositions for the treatment of a variety of diseases and conditions. 1. A method of treating gout comprising co-administration of 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 ,2 ,4-triazol-3-ylthio)acetate , or a pharmaceutically acceptable salt thereof , and colchicine to a subject.2. The method of claim 1 , wherein said method provides greater mean gout flare reduction than co-administration of colchicine and a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.3. The method of claim 1 , wherein the total dosage of colchicine administered during co-administration with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least 50% less than the total dosage of colchicine that would be required for a similar effect when co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.4. The method of claim 1 , wherein the amount of time that colchicine is co-administered with 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1 claim 1 ,2 claim 1 ,4-triazol-3-ylthio)acetate claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , is at least one week less than would be required for a similar effect when colchicine is co-administered with a therapeutic agent that is not a dual inhibitor of URAT1 and an inflammasome.5. A method of reducing monosodium urate induced inflammation in a subject in need thereof claim 1 , the method comprising administering a pharmaceutical composition comprising a pharmaceutical agent having both uricosuric and anti-inflammatory activity.6. The method of wherein the pharmaceutical agent is a URAT1 inhibitor with anti-inflammatory activity.7. The method of wherein the pharmaceutical agent is 2-(5-bromo-4-(4 ...

Pharmaceutical combinations of n-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamide as inhibitors of mek and methods of use

This invention concerns N-(2-arylamino) aryl sulfonamide compounds which are inhibitors of MEK including crystalline polymorphic forms which exhibit a specific powder x-ray diffraction profile and/or a specific differential scanning calorimetry profile. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer, hyperproliferative diseases and inflammatory conditions. The invention also concerns methods of making the compounds and compositions described herein.

Hypertension and hyperuricemia

A method for treating hypertension in a subject in need thereof (e.g., wherein said treatment does not result in an increase in serum uric acid levels, abnormally elevated serum uric acid levels, hyperuricemia, serum uric acid levels of above 6 mg/dL, or in the development of gout in the subject), the method comprising administering to the subject: a. a thiazide diuretic; and b. an organic anion transporter 4 (OAT4) inhibitor. The thiazide diuretic is selected from hydrochlorothiazide, bendroflumethiazide, benzothiadiazine, hydroflumethiazide, clorothiazide, methyclothiazide, polythiazide, chlorthalidone, metolazone, indapamide, bumetanide, ethacrynic acid, furosemide or torsemide. The OAT4 inhibitor is 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)- 4H-1,2,4-triazol-3-ylthio)acetic acid or a pharmaceutically acceptable salt thereof.

Treatment of gout and hyperuricemia

Combinations of mek inhibitors and raf kinase inhibitors and uses thereof

Treatment of gout and hyperuricemia

Memory control circuit permitting microcomputer system to utilize static and dynamic rams

MEMORY CONTROL CIRCUIT PERMITTING MICROCOMPUTER SYSTEM TO ULITIZE STATIC AND DYNAMIC RAMS Abstract A memory accessing control for a microcomputer system is compatible with both static and dynamic type memories. A gating circuit is responsive to read/write and address latch enable control signals of a microprocessor, and provides an enable signal utilized to generate a chip enable signal compatible with the timing and control requirements of both dynamic and static memories.

Combinations of mek inhibitors and raf kinase inhibitors and uses thereof

This invention concerns combinations of inhibitors of MEK, Raf protein kinases, and other kinases includin VEG-FR1 -3 and PDGFR-.beta... This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer and other hyperproliferative disorders.

Derivatives of n-(arylamino) sulfonamides including polymorphs as inhibitors of mek as well as compositions, methods of use and methods for preparing the same

This invention concerns N-(2-arylamino) aryl sulfonamide compounds which are inhibitors of MEK including crys-talline polymorphic forms which exhibit a specific powder x-ray diffraction profile and/or a specific differential scanning calorimetry profile. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer, hyperprolif-erative diseases and inflammatory conditions. The invention also concerns methods of making the compunds and compositions described herein.

Derivatives of N-(arylamino) sulfonamides including polymorphs as inhibitors of MEK as well as compositions, methods of use and methods for preparing the same

Treatment of gout and hyperuricemia.

Sodyum 2-(5-bromo-4-(4-siklopropilnaftalen-1-il)-4H-1,2,4-triazol-3-iltiyo)asetat açıklanmıştır. Ek olarak, çeşitli hastalıklar ve durumların tedavisi için farmasötik bileşimler ve bu tür bileşimlerin kullanımları da açıklanmıştır. Sodium 2- (5-bromo-4- (4-cyclopropylnaphthalen-1-yl) -4H-1,2,4-triazol-3-ylthio) acetate is disclosed. In addition, pharmaceutical compositions for the treatment of various diseases and conditions and uses of such compositions are disclosed.

Treatment of gout and hyperuricemia

Hypertension and hyperuricemia

Μία μέθοδος για την θεραπεία της υπέρτασης σε ένα άτομο που την έχει ανάγκη (π.χ., όπου η εν λόγω θεραπεία δεν έχει σαν αποτέλεσμα μία αύξηση στα επίπεδα ουρικού οξέος ορού, τα ανώμαλα αυξημένα επίπεδα ουρικού οξέος ορού, την υπερουριχαιμία, τα επίπεδα ουρικού οξέος ορού πάνω από 6 mg/dL, ή την ανάπτυξη ουρικής αρθρίτιδας στο άτομο), όπου η μέθοδος περιλαμβάνει χορήγηση στο άτομο: a. Ενός θειαζιδικού διουρητικού, και b. Ενός καταστολέα μεταφοράς οργανικού ανιόντος 4 (ΟΑΤ4). Το θειαζιδικό διουρητικό επιλέγεται από Υδροχλωροθειαζίδη, βενδροφλουμεθειαζίδη, βενζοθειαδιαζίνη, υδροφλουμεθειαζίδη, χλωροθειαζίδη, μεθυκλοθειαζίδη, πολυθειαζίδη, χλωροταλιδόνη, μετολαζόνη, ινδαπαμίδη, βουμετανίδη, αιθακρυνικό οξύ, φουροσεμίδη ή τορσεμίδη. Ο καταστολέας ΟΑΤ4 είναι 2-(5-bromo-4-(4-cyclopropylnaphthalen-l-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid ή ένα φαρμακευτικά αποδεκτό άλας αυτού. One method for treating hypertension in a person in need (e.g., where said treatment does not result in an increase in serum uric acid levels, abnormally elevated serum uric acid levels, hyperuricemia, levels serum uric acid above 6 mg / dL, or the development of gout in the subject), wherein the method comprises administering to the subject: a. A thiazide diuretic, and b. An Organic Anion Transport Suppressor 4 (CAT4). The thiazide diuretic is selected from Hydrochlorothiazide, benthoflumethiazide, benzothiadiazine, hydroflumethiazide, chlorothiazide, methylclothiazide, polythiazide, chlorotalidone, metolazone, indomethacid, indapamide, indapamide, indapamide, The CAT4 suppressor is 2- (5-bromo-4- (4-cyclopropylnaphthalen-1-yl) -4H-1,2,4-triazol-3-ylthio) acetic acid or a pharmaceutically acceptable salt thereof.

Esophageal dilation bougie

An esophageal dilation bougie (10) comprises a hollow, flexible, tube (12) filled with a dispersion of tungsten particles in a silicone material for treating cardiospasm, esophagitis, stenosis and other esophageal diseases.

Hypertension and hyperuricemia

Derivatives of n-(arylamino) sulfonamides including polymorphs as inhibitors of mek as well as compositions, methods of use and methods for preparing the same

This invention concerns N-(2-arylamino) aryl sulfonamide compounds which are inhibitors of MEK including crystalline polymorphic forms which exhibit a specific powder x-ray diffraction profile and/or a specific differential scanning calorimetry profile. This invention also concerns pharmaceutical compositions comprising the compounds described herein and methods of use of the compounds and compositions described herein, including the use in the treatment and/or prevention of cancer, hyperproliferative diseases and inflammatory conditions. The invention also concerns methods of making the compunds and compositions described herein.

TREATMENT OF URINARY ARTHRITIS AND HYPOTHESIS

Περιγράφεται το 2-(5-βρωμο-4-(4-κυκλοπροπυλοναφθαλιν-1-υλ)-4Η-1,2,4-τριαζολ-3-υλοθειο) οξικό άλας. Επιπλέον, περιγράφονται φαρμακευτικές συνθέσεις και οι χρήσεις τέτοιων συνθέσεων για τη θεραπεία μιας ποικιλίας ασθενειών και παθήσεων. The 2- (5-bromo-4- (4-cyclopropylonaphthalin-1-yl) -4H-1,2,4-triazol-3-ylthio) acetate is described. In addition, pharmaceutical compositions and uses of such compositions for the treatment of a variety of diseases and conditions are described.

Dilatationsbougie für die speiseröhre

Use of a ppar-delta agonist in the treatment of kidney disease

Systems and methods for ex vivo culture of podocytes and uses thereof

Among the various aspects of the present disclosure is the provision of systems and methods for growing or culturing podocytes and uses thereof. In one aspect, a podocyte culture system including an ECM-patterned substrate is disclosed. The ECM-patterned substrate includes a compliant substrate. The compliant substrate includes a predetermined stiffness ranging from about 0.1 kPa to about 10 kPa. The ECM-patterned substrate further includes a plurality of patterned elements deposited over an exposed surface of the compliant substrate.

Use of a ppar-delta agonist in the treatment of kidney disease

Described herein is the use of a PPAR-delta agonist in the treatment of kidney diseases, wherein: the kidney disease is Alport syndrome, Goodpasture syndrome, thin basement membrane nephropathy (TBMN), focal segmental glomerulosclerosis (FSGS), benign familial hematuria (BFH), post-transplant anti-GBM (Glomerular Basement Membrane) nephritis, X-linked Alport syndrome (XLAS), autosomal recessive Alport syndrome (ARAS) or autosomal dominant Alport syndrome (ADAS).

Cxcr-2 inhibitors for treating crystal arthropathy disorders

N-(2-((2,3-difluorobenzyl)thio)-6-(((2R,3S)-3,4-dihydroxybutan-2-yl)oxy)pyrimidin-4-yl)azetidine-1-sulfonamide (compound 3) and N-(6-(((2R,3S)-3,4-dihydroxy butan-2-yl)oxy)-2-((4-fluoro benzyl)thio)pyrimidin-4-yl)-3-methylazetidine-1-sulfonamide(compound 4) are known chemokine modulators and are therefore useful in the treatment of diseases/conditions in which modulation of chemokine receptor activity is beneficial. In particular, provided herein are compositions and methods for the treatment and prevention of gout.

Inhibidores de cxcr-2 para tratamiento de trastornos de artropatía por cristales

El N-(2-((2,3-difluorobencil)tio)-6-(((2R,3S)-3,4-dihidroxibutan-2-il)oxi)pirimidin-4-il)azetidin-1-sulfonamida (compuesto 3) y N-(6-(((2R,3S)-3,4-dihidroxi butan-2-il)oxi)-2-((4-fluoro bencil)tio)pirimidin-4-il)-3-metilazetidin-1-sulfonamida (compuesto 4) son moduladores de quimiocina conocidos y por lo tanto son útiles en el tratamiento de enfermedades/afecciones en las cuales es benéfica la modulación de la actividad del receptor de quimiocina. En particular, se proporcionan en la presente compuesto y métodos para el tratamiento y prevención de la gota. Compuesto 3 Compuesto 4