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: The disclosure relates to a method for treatment of cancer comprising administering to a subject in need thereof a first agent in a therapeutically effective amount and a second agent in a therapeutically effective amount. Preferably, the first agent comprises an EZH2 inhibitor, e.g., tazemetostat or a pharmaceutically acceptable salt thereof. In certain embodiments, the methods of the disclosure are used to treat breast cancer, ovarian cancer, or both.

Abstract: The present disclosure provides methods and pharmaceutical compositions for treating or slowing the progression of cancer, i.e., pancreatic cancer or esophageal cancer, by administering to a human subject in need thereof a therapeutically effective amount of an inhibitor of the histone methyltransferase, SETD2.

Abstract: Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula: wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

Abstract: Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula: wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

Abstract: The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The disclosure provides a method for treating cancer in a subject in need thereof comprising administering to the subject: (a) a therapeutically effective amount of an EZH2 inhibitor and (b) a therapeutically effective amount of an immune checkpoint inhibitor. In certain embodiments of the methods of the disclosure, the EZH2 inhibitor is tazemetostat.

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: Provided herein are compounds of Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, wherein X, R1, R1a, R2a, R2b, R2c, R2d, are as defined herein, and Ring HET is a 6-membered monocyclic heteroaryl ring system of Formula: wherein L2, R13, G8, G10, G11, and G12 are as defined herein. Compounds of the present invention are useful for inhibiting CARM1 activity. Methods of using the compounds for treating CARM1-mediated disorders are also described.

Abstract: The present disclosure provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.

Abstract: The present disclosure relates to a method of preventing or treating a cancer via administering an EHMT2 inhibitor or a combination comprising an EHMT2 inhibitor compound and one or more additional therapeutic agent disclosed herein or a pharmaceutical composition thereof to subjects in need thereof. The present disclosure also relates to the use of such compounds or combinations for research or other non-therapeutic purposes.

Abstract: The present invention relates to 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 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 compositions comprising inhibitors of human histone methyltransferase EZH2 and their use for the treatment of cancer.

Abstract: The present disclosure relates to methods of a malignant rhabdoid tumor (MRT), a rhabdoid tumor of the kidney (RTK), an atypical teratoid/rhabdoid tumor (AT/RT), an epithelioid malignant peripheral nerve sheath tumor, a myoepithelial carcinoma, and/or a renal medullary carcinoma by using an EZH2 inhibitor in combination with one or more additional treatment modalities.

Abstract: The present disclosure provides SETD2 protein inhibitors, and methods, compositions, and kits for treating diseases, disorders, or conditions in a subject with a SETD2 protein inhibitor and, optionally, a second therapeutic agent, wherein the second therapeutic agent comprises one or more glucocorticoid receptor agonists, one or more immunomodulatory drugs, one or more proteasome inhibitors, one or more Bcl-2 inhibitors, one or more pleiotropic pathway modulators, one or more XPO1 inhibitors, one or more histone deacetylase inhibitors, or one or more EZH2 inhibitors, or a combination thereof.

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: The disclosure provides methods of treating, identifying and/or selecting for treatment a subject having a cancer in which an immune checkpoint protein is upregulated. In certain embodiments, the methods for treating cancer in a subject in need thereof comprise administering to the subject: (a) a therapeutically effective amount of an EZH2 inhibitor and (b) a therapeutically effective amount of an immune checkpoint inhibitor. In certain embodiments of the methods of the disclosure, the EZH2 inhibitor is tazemetostat.

Abstract: The present disclosure provides novel cancer therapies. The treatment of cancers harboring EP300 mutations with CREBBP inhibition therapy is 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.