Salt form of a human histone methyltransferase EZH2 inhibitor
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.
1. A method of treating a cancer, comprising administering to a subject in need thereof a therapeutically effective amount of a polymorph of 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, wherein the polymorph exhibits an X-ray powder diffraction pattern having a peak at 10.1+/−0.3 degrees and one or more characteristic peaks expressed in degrees 2-theta selected from peaks at about 17.5+/−0.3 degrees and about 22.0+/−0.3 degrees 2-theta.
2. The method of claim 1 , wherein the cancer is lymphoma, leukemia, melanoma, sarcoma, prostate cancer, or breast cancer.
3. The method of claim 2 , wherein the cancer is lymphoma.
4. The method of claim 3 , wherein the lymphoma is non-Hodgkin lymphoma, follicular lymphoma, or diffuse large B-cell lymphoma (DLBCL).
5. The method of claim 4 , wherein the lymphoma is non-Hodgkin lymphoma.
6. The method of claim 4 , wherein the lymphoma is follicular lymphoma.
7. The method of claim 4 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL).
8. The method of claim 2 , wherein the cancer is sarcoma.
9. The method of claim 8 , wherein the sarcoma is selected soft tissue sarcoma, osteosarcoma, rhabdomyosarcoma, Kaposi sarcoma, uterine sarcoma, or a sarcoma belonging to the Ewing family of sarcoma tumors.
10. A method of treating follicular lymphoma, comprising administering to a subject in need thereof a therapeutically effective amount of a polymorph of 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, wherein the polymorph exhibits an X-ray powder diffraction pattern having one or more characteristic peaks expressed in degrees 2-theta selected from peaks at about 10.1+/−0.3 degrees, about 17.5+/−0.3 degrees, and about 22.0+/−0.3 degrees 2-theta.