SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses. 295-. (canceled)98. A conjugate of a compound of .99. The conjugate claim 98 , wherein the conjugate protein is CRM.100. The conjugate of claim 98 , wherein the conjugate protein is GBS.101. A vaccine comprising a conjugate of .102. A conjugate of a compound of .103. A vaccine comprising a conjugate of .104. A vaccine comprising a conjugate of .105. A therapeutic protein comprising a compound of .106. A therapeutic protein comprising a compound of .107. An imaging agent comprising a compound of .108. An imaging agent comprising a compound of .109. A labeling tool comprising a compound of .110. A labeling tool comprising a compound of . The present invention relates generally to a novel method of introducing modifying groups to a protein. In particular, the present invention relates to the selective derivation of lysine residues in proteins using a chemoenzymatic microbial transglutaminase-mediated reaction for modifying proteins and methods for their preparation and use.It is well-known that the properties and characteristics of proteins may be modified by conjugating groups to the protein. For example, U.S. Pat. No. 4,179,337 disclosed proteins conjugated to polyethylene or polypropylene glycols. Generally, such conjugation generally requires some functional group in the protein to react with another functional group in a conjugating group. Amino groups, such as the N-terminal amino group or the ε-amino group in lysine residues have been used in combination with suitable acylating reagents for this purpose. It is often desired or necessary to control the conjugation reaction, such as where the conjugating compounds are attached to the protein and to control how many ...

SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses. 197-. (canceled)99. The conjugate of claim 98 , wherein the conjugate protein is CRM.100. The conjugate of claim 98 , wherein the conjugate protein is GBS.101. (canceled)103. The conjugate of claim 98 , wherein W is polyethylene glycol having a molecular weight of between about 40 and about 80 claim 98 ,000 amu.105. The conjugate of claim 98 , wherein Ris a fatty acid.107. The conjugate of claim 106 , wherein the fluorophore is selected from a fluorescein claim 106 , rhodamine claim 106 , a Cy dye claim 106 , an Alexa dye claim 106 , and a coumarin. This application is a divisional of U.S. application Ser. No. 16/204,557, filed on Nov. 29, 2018, which is a divisional of U.S. application Ser. No. 15/144,397, filed on May 2, 2016, which is a divisional of U.S. patent application Ser. No. 14/329,758, now U.S. Pat. No. 9,359,400, filed Jul. 11, 2014, which claims the benefit of the filing date under 35 U.S.C. § 119(e) of Provisional U.S. Patent Application No. 62/016,044, filed Jun. 23, 2014, and of Provisional U.S. Patent Application No. 61/845,273, filed Jul. 11, 2013, the entire contents of each of which are incorporated herein by reference in their entireties.The present invention relates generally to a novel method of introducing modifying groups to a protein. In particular, the present invention relates to the selective derivation of lysine residues in proteins using a chemoenzymatic microbial transglutaminase-mediated reaction for modifying proteins and methods for their preparation and use.The contents of the text file named “PAT055641-US-DIV03_seq_lst_ST25.txt,” which was created on Nov. 29, 2018 and is 10 KB in size, are hereby incorporated by reference in their ...

SITE-SPECIFIC CHEMOENZYMATIC PROTEIN MODIFICATIONS

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses. 2. The method of claim 1 , wherein x is 1.413-. (canceled)16. The method of claim 15 , wherein y is 0 and z is 1.17. The method of claim 15 , wherein y is 1 and z is 1.1820-. (canceled)21. The method of claim 15 , wherein W is polyethylene glycol having a molecular weight of between about 40 and about 3000 amu.2223-. (canceled)24. The method of claim 15 , wherein Ris linear or branched C-Calkyl-N.2527-. (canceled)29. The method of claim 1 , wherein Ris a fluorophore.29. (canceled)31. The method of claim 1 , wherein Ris a polysaccharide.3235-. (canceled)44. The method of claim 1 , wherein Ris a fatty acid.45101-. (canceled) The application is a continuation of U.S. application Ser. No. 15/144,397, filed on May 2, 2016, which is a divisional of U.S. patent application Ser. No. 14/329,758, now U.S. Pat. No. 9,359,400, filed Jul. 11, 2014, which claims the benefit of the filing date under 35 U.S.C. § 119(e) of Provisional U.S. Patent Application No. 62/016,044, filed Jun. 23, 2014, and of Provisional U.S. Patent Application No. 61/845,273, filed Jul. 11, 2013, the entire contents of each of which are incorporated herein by reference in their entireties.The present invention relates generally to a novel method of introducing modifying groups to a protein. In particular, the present invention relates to the selective derivation of lysine residues in proteins using a chemoenzymatic microbial transglutaminase-mediated reaction for modifying proteins and methods for their preparation and use.The contents of the text file named “PAT055641-US-CNT_seq_1st_ST25.txt,” which was created on Nov. 29, 2018 and is 10 KB in size, are hereby incorporated by reference in their entireties.It is ...

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione Derivatives and Uses thereof

The present disclosure relates to compounds of formula (I′) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Site-specific chemoenzymatic protein modifications

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

Site-specific chemoenzymatic protein modifications

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

Lysine-specific chemoenzymatic protein modifications using microbial transglutaminase

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

Site-specific chemoenzymatic protein modifications

The present invention relates to methods and reagents for use in site-selective modification of proteins having lysine residues with functionalized peptides using a chemoenzymatic microbial transglutaminase-mediated reaction. The functionalized proteins may be used for study or therapeutic uses.

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

La presente divulgación se relaciona con composiciones farmacéuticas y compuestos de fórmula (I’) y con su uso para reducir los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y para el tratamiento de trastornos sanguíneos hereditarios (<em>por ejemplo,</em> hemoglobinopatías, <em>por ejemplo,</em> beta-hemoglobinopatías), tales como la enfermedad de células falciformes y la beta-talasemia.

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

The present disclosure relates to compounds of formula (I') and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Compositions and methods for the treatment of hemoglobinopathies

The present invention is directed to compositions and methods for the treatment of hemoglobinopathies.

Lysine-specific chemoenzymatic protein modifications using microbial transglutaminase

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

The present disclosure relates to compounds of formula (I') and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

The present disclosure relates to compounds of formula (I') and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Compositions and methods for the treatment of hemoglobinopathies

The present invention is directed to compositions and methods for the treatment of hemoglobinopathies.

COMPOUNDS DERIVED FROM 3- (5-METOXY-1-OXOISOINDOLIN-2-IL) PIPERIDIN-2,6-DIONA, METHODS OF USING THEM AND PHARMACEUTICAL COMBINATIONS

La presente divulgación se relaciona con composiciones farmacéuticas y compuestos de fórmula (I) y con su uso para reducir los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y para el tratamiento de trastornos sanguíneos hereditarios (hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y la beta-talasemia.

DERIVATIVES OF 3-(5-METHOXY-1-OXOISOINDOLIN-2-IL)PIPERIDIN-2,6-DIONE AS REDUCERS OF THE ACTIVITY OF WIZ PROTEIN

Compuestos derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona y su empleo en la reducción de los niveles de expresión de la proteína Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), composiciones farmacéuticas que los comprenden y su uso para el tratamiento de enfermedades del fluido sanguíneo tales como b-talasemia, b-hemoglobinopatía o la enfermedad de células falciformes. Reivindicación 1: Un compuesto de fórmula (1) o una sal, hidrato, solvato, profármaco, estereoisómero, y tautómero farmacéuticamente aceptable del mismo, en donde: Y se selecciona de O, CH₂, CF₂, y CHF; z es un entero de 0 a 2; RX¹ y RX² se seleccionan cada uno independientemente de hidrógeno y alquilo C₁₋₆; RY¹ y RY² se seleccionan cada uno independientemente de hidrógeno y alquilo C₁₋₆; RZ¹ y RZ² son ambos hidrógeno o 1 de RZ¹ y RZ² y 1 de RY¹ y RY² conjuntamente forman un grupo puente de alquileno C₁₋₂ y el otro de RZ¹ y RZ² y RY¹ y RY² son ambos hidrógeno; R¹ se selecciona de hidrógeno y alquilo C₁₋₆; R² se selecciona de hidrógeno, -C(=O)-R³, cicloalquilo C₃₋₈, haloalquilo C₁₋₆, y alquilo C₁₋₁₀, en donde el alquilo está sustituido con 0 - 1 sustituyente independientemente seleccionado de arilo C₆₋₁₀, heteroarilo de 5 a 10 miembros que comprende 1 - 4 heteroátomos independientemente seleccionados de N, O, y S, heterociclilo de 4 a 11 miembros que comprende 1 - 2 heteroátomos independientemente seleccionados de N, O, y S, cicloalquilo C₃₋₈ y -O-(R²ᵃ), en donde el arilo, heteroarilo, heterociclilo, y cicloalquilo están cada uno independientemente sustituidos con 0 - 5 R⁴; R²ᵃ es alquilo C₁₋₆ en donde el alquilo está sustituido con 0 - 1 sustituyente independientemente seleccionado de arilo C₆₋₁₀; R³ se selecciona de -CH=CR³ᵃR³ᵇ, arilo C₆₋₁₀, heteroarilo de 5 a 10 miembros que comprende 1 - 4 heteroátomos independientemente seleccionados de N, O, y S, heterociclilo de 4 a 6 miembros que comprende 1 - 2 heteroátomos independientemente seleccionados de N, O, y S, ...

Derivados de 3–(1–oxoisoindolin–2–il)piperidina–2,6–diona y sus usos médicos

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Derivados de pirazolopiridina y sus usos

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Derivados de 3–(1–oxoisoindolin–2–il)piperidina–2,6–diona y sus usos médicos

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and medical uses thereof

The application relates to compounds of formula (I), pharmaceutical compositions comprising them and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta- hemoglobinopathies), such as sickle cell disease and beta- thalassemia.

3-(5-methoxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

Derivados de pirazolopiridina y sus usos

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Benzisoxazole derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders ( e.g. , hemoglobinopathies, e.g ., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Pyrazolopyridine derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona y usos de los mismos.

La presente divulgación se relaciona con composiciones farmacéuticas y compuestos de fórmula (I') y con su uso para reducir los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y para el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y la beta-talasemia.

Systems, Devices, and Methods for Uterine Hemostasis

A device may include a flexible tube comprising: a distal end, a proximal tip, the proximal tip comprising a suction line extension being configured for placement in a uterine cavity of a uterus after childbirth, a tube center of the flexible tube; and at least one lumen around the tube center, the at least one lumen comprising a suction line, the suction line being in communication with a source of negative pressure and the suction line extension, the suction line extension being configured for applying the negative pressure to the uterine cavity using the source of the negative pressure thereby causing mechanical hemostasis of bleeding blood vessels of a uterine wall of the uterine cavity. Embodiments include an anchoring mechanism being proximate to the suction line extension along the flexible tube, the anchoring mechanism being configured for maintaining the suction line extension in a desired position within the uterine cavity.

3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and medical uses thereof

The application relates to compounds of formula (I), pharmaceutical compositions comprising them and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta- hemoglobinopathies), such as sickle cell disease and beta- thalassemia.

Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos médicos

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Systems, devices, and methods for uterine hemostasis

A device may include a flexible tube comprising: a distal end, a proximal tip, the proximal tip comprising a suction line extension being configured for placement in a uterine cavity of a uterus after childbirth, a tube center of the flexible tube; and at least one lumen around the tube center, the at least one lumen comprising a suction line, the suction line being in communication with a source of negative pressure and the suction line extension, the suction line extension being configured for applying the negative pressure to the uterine cavity using the source of the negative pressure thereby causing mechanical hemostasis of bleeding blood vessels of a uterine wall of the uterine cavity. Embodiments include an anchoring mechanism being proximate to the suction line extension along the flexible tube, the anchoring mechanism being configured for maintaining the suction line extension in a desired position within the uterine cavity.

Systems, devices, and methods for uterine hemostasis

A device may include a flexible tube comprising: a distal end, a proximal tip, the proximal tip comprising a suction line extension being configured for placement in a uterine cavity of a uterus after childbirth, a tube center of the flexible tube; and at least one lumen around the tube center, the at least one lumen comprising a suction line, the suction line being in communication with a source of negative pressure and the suction line extension, the suction line extension being configured for applying the negative pressure to the uterine cavity using the source of the negative pressure thereby causing mechanical hemostasis of bleeding blood vessels of a uterine wall of the uterine cavity. Embodiments include an anchoring mechanism being proximate to the suction line extension along the flexible tube, the anchoring mechanism being configured for maintaining the suction line extension in a desired position within the uterine cavity.

Derivados de 3-(5-oxoisoindolin-2-il)piperidina-2,6-diona e seus usos

derivados de 3-(5-oxoisoindolin-2- il)piperidina-2,6-diona e seus usos. a presente invenção refere-se a compostos da fórmula (i), composições farmacêuticas compreendendo os mesmos e seu uso na redução dos níveis de expressão de motivos de dedo de zinco amplamente interespaçados (wiz) ou na indução da expressão da hemoglobina fetal (hbf) e no tratamento de disfunções sanguíneas hereditárias (p. ex., hemoglobinopatias, p. ex., beta-hemoglobinopatias), tais como doença das células falciformes e beta-talassemia.

Pyrazolopyridine Derivatives and Uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Compositions and methods for the treatment of hemoglobinopathies

The present invention is directed to compositions and methods for the treatment of hemoglobinopathies.

Derivados de pirazolopiridina y sus usos

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Derivados de pirazolopiridina y sus usos.

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y beta-talasemia.

Pyrazolopyridine derivatives and uses thereof

Derivados de pirazolopiridina y sus usos

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Derivados de pirazolopiridina y sus usos.

La presente divulgación se refiere a compuestos de Fórmula (I) y composiciones farmacéuticas y su uso en la reducción de los niveles de expresión de los Motivos de Dedos de Zinc Ampliamente Interespaciados (WIZ), o en la inducción de la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos de la sangre hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y beta-talasemia.

Derivados de pirazolopiridina e usos dos mesmos

derivados de pirazolopiridina e usos dos mesmos. a presente invenção refere-se a compostos de fórmula (i) e composições farmacêuticas e seu uso na redução dos níveis de expressão de motivos de dedo de zinco amplamente interespaçados (wiz) ou na indução de expressão de hemoglobina fetal (hbf) e no tratamento dos distúrbios sanguíneos hereditários (por exemplo, hemoglobinopatias, por exemplo, beta-hemoglobinopatias), tal como doença da célula falciforme e beta-talassemia.

Pyrazolopyridine derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Systems, Devices, and Methods for Uterine Hemostasis

A device may include a flexible tube comprising: a distal end, a proximal tip, the proximal tip comprising a suction line extension being configured for placement in a uterine cavity of a uterus after childbirth, a tube center of the flexible tube; and at least one lumen around the tube center, the at least one lumen comprising a suction line, the suction line being in communication with a source of negative pressure and the suction line extension, the suction line extension being configured for applying the negative pressure to the uterine cavity using the source of the negative pressure thereby causing mechanical hemostasis of bleeding blood vessels of a uterine wall of the uterine cavity. Embodiments include an anchoring mechanism being proximate to the suction line extension along the flexible tube, the anchoring mechanism being configured for maintaining the suction line extension in a desired position within the uterine cavity.

Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos medicos.

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y beta-talasemia.

Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos medicos

Referido a compuestos derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona de formula I', o una de sus sales, hidratos, solvatos, profarmacos, estereoisomeros o tautomeros farmaceuticamente aceptables, donde: cada R1 se selecciona de manera independiente de H, C1-C6alquilo, hidroxilo, entre otros; R2 se selecciona de H, C3-C11cicloalquilo, heterociclilo de 4 a 11 miembros que comprende 1-2 heteroatomos seleccionados de manera independiente de N, O, y S, C1-C6haloalquilo, entre otros; n es 0, 1, 2, 3, 4 o 5; y m es 0, 1 o 2. Estos compuestos reducen los niveles de expresion de proteinas que contiene de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresion de la hemoglobina fetal (HbF). Tambien se refiere a la preparacion de dichos compuestos, sus compuestos intermedios, una composicion farmaceutica que comprende dichos compuestos y su uso en el tratamiento de trastornos sanguineos hereditarios, como hemoglobinopatias, beta-hemoglobinopatias, enfermedad de celulas falciformes y beta-talasemia.

Derivados de 3–(1–oxoisoindolin–2–il)piperidina–2,6–diona y sus usos médicos

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta–hemoglobinopatías), tales como la enfermedad de células falciformes y beta–talasemia.

Derivados de 3-(5-oxi)-1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos

La presente divulgación se refiere a compuestos de fórmula (1) y composiciones farmacéuticas y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, b-hemoglobinopatías), tales como la enfermedad de células falciformes y b-talasemia. Un compuesto de fórmula (1’) o una de sus sales, hidratos, solvatos, profármacos, estereoisómeros o tautómeros farmacéuticamente aceptables. Un compuesto de fórmula (1’’) o una de sus sales, hidratos, solvatos, profármacos, estereoisómeros o tautómeros farmacéuticamente aceptables. Un compuesto de fórmula (1) o una de sus sales, hidratos, solvatos, profármacos, estereoisómeros o tautómero farmacéuticamente aceptables. Un compuesto un compuesto de fórmula (Y).

3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and medical uses thereof

The application relates to compounds of formula (I), pharmaceutical compositions comprising them and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta- hemoglobinopathies), such as sickle cell disease and beta- thalassemia.

Derivados de 3-(1-oxoisoindolin-2-il)piperidina-2,6-diona y sus usos médicos

La presente solicitud se refiere a compuestos de fórmula (I), composiciones farmacéuticas que los comprenden, y su uso para reducir los niveles de expresión de los motivos de dedos de zinc ampliamente interespaciados (WIZ), o para inducir la expresión de la hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como la enfermedad de células falciformes y beta-talasemia.

Pyrazolopyridine derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (

3-(5-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia.

Pyrazolopyridine derivatives and uses thereof

The present disclosure relates to compounds of formula (I) and pharmaceutical compositions and their use in reducing Widely Interspaced Zinc Finger Motifs (WIZ) expression levels, or inducing fetal hemoglobin (HbF) expression, and in the treatment of inherited blood disorders (e.g., hemoglobinopathies, e.g., beta-hemoglobinopathies), such as sickle cell disease and beta-thalassemia

Derivados de 3-(5-metoxi-1-oxoisoindolin-2-il)piperidin-2,6-diona y usos de los mismos

La presente divulgación se refiere a compuestos de fórmula (I') y composiciones farmacéuticas y su uso para reducir los niveles de expresión de motivos de dedos de zinc ampliamente interespaciados (WIZ), o inducir la expresión de hemoglobina fetal (HbF), y en el tratamiento de trastornos sanguíneos hereditarios (por ejemplo, hemoglobinopatías, por ejemplo, beta-hemoglobinopatías), tales como enfermedad de células falciformes y beta-talasemia. (Traducción automática con Google Translate, sin valor legal)