Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

Abstract: This disclosure generally relates to pyridine-2-one compounds of formula (I) and methods of using them in the treatment of a disorder, such as cancer or a SMARCA2-associated disorder, including as antagonists (e.g., inhibitors) of SMARCA2. The present disclosure provides treatment modalities, e.g., strategies, treatment methods, patient stratification methods, compounds, combinations, and compositions that are useful for the treatment of disorders, e.g., proliferative disorders, such as certain cancers. Some aspects of this disclosure provide treatment modalities, methods, strategies, compounds, compositions, combinations, and dosage forms for the treatment of cell proliferative disorders, e.g., cancers with decreased activity or function, or loss of function, of SMARCA4 with a SMARCA2 antagonist.

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Abstract: The disclosure relates to methods, compounds for use and medicaments for the treatment of cancer comprising administering to a subject in need thereof a first agent in a therapeutically effective amount and one or more second agents each in a therapeutically effective amount. In some embodiments, the first agent comprises an EZH2 inhibitor. In certain embodiments, the first agent is tazemetostat or a pharmaceutically acceptable salt thereof and the methods of the disclosure are used to treat lung cancer, e.g., non-small cell lung cancer.

Abstract: The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Abstract: The present disclosure provides novel compounds, compositions comprising the compounds and methods of use thereof.

Abstract: The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

Abstract: The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, for example, modulators of CD40 pathway activity, such as CD40 agonists, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Abstract: The present invention relates to aryl- or heteroaryl-substituted benzene compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating cancer by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.

Abstract: The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents (such as tyrosine kinase inhibitors or VEGF/VEGFR inhibitors), particularly anticancer agents such as sunitinib, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting PRMT5 activity. Methods of using the compounds for treating PRMT5-mediated disorders are also described.

Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

Abstract: The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

Abstract: The present disclosure relates to pharmaceutical compositions comprising inhibitor(s) of human histone methyltransferase EZH2, and methods of cancer therapy using the EZH2 inhibitor(s).

Abstract: The present invention relates to methods of treating disorders in which DOT1L-mediated protein methylation plays a part, such as cancer, by administering DOT1L inhibitor compounds and pharmaceutical compositions to subjects in need thereof.

Abstract: Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

Abstract: Described herein are compounds of Formula (I), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds described herein are useful for inhibiting arginine methyltransferase activity. Methods of using the compounds for treating arginine methyltransferase-mediated disorders are also described.

Abstract: The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.