Method for treating cancer
View Patent ↗The present invention relates to pharmaceutical compositions comprising inhibitor(s) of human histone methyltransferase EZH2, and methods of cancer therapy using the EZH2 inhibitor(s).
1. A solid pharmaceutical formulation comprising
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:
in an amount of about 49 wt. %, or a salt of Compound 1 in an amount equivalent to about 49 wt. % of Compound 1, or a combination of Compound 1 and a salt of Compound 1 wherein the combination is present in an amount equivalent to about 49 wt. % of Compound 1;
lactose monohydrate in an amount of about 17 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 15 wt. %;
sodium starch glycolate in an amount of about 5 wt. %;
hydroxypropyl cellulose in an amount of about 4 wt. %; and
magnesium stearate in an amount of about 2 wt. %.
2. A solid pharmaceutical formulation consisting 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:
in an amount of about 40-60 wt. %, or a salt of Compound 1 in an amount equivalent to about 40-60 wt. % of Compound 1, or a combination of Compound 1 and a salt of Compound 1 wherein the combination is present in an amount equivalent to about 40-60 wt. % of Compound 1;
lactose monohydrate in an amount of about 10-20 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 11-19 wt. %;
sodium starch glycolate in an amount of about 3-7 wt. %;
hydroxypropyl cellulose in an amount of about 1-10 wt. %;
magnesium stearate in an amount of about 0.5-5 wt. %; and
a coating composition in an amount of about 1-10 wt. %.
3. The solid pharmaceutical formulation of claim 2 , wherein the coating composition comprises hypromellose, talc, macrogol, titanium dioxide, and iron (III) oxide.
4. The solid pharmaceutical formulation of claim 1 , further comprising a coating composition.
5. The solid pharmaceutical formulation of claim 4 , wherein the coating composition comprises hypromellose, talc, macrogol, titanium dioxide, and iron (III) oxide.
6. The solid pharmaceutical formulation of claim 1 , wherein the pharmaceutical composition comprises Compound 1 in an amount of about 49 wt. %.
7. The solid pharmaceutical formulation of claim 1 , wherein the pharmaceutical composition comprises a salt of Compound 1 in an amount equivalent to about 49 wt. % of Compound 1.
8. The solid pharmaceutical formulation of claim 7 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.
9. The solid pharmaceutical formulation of claim 1 , wherein the pharmaceutical composition comprises a combination of Compound 1 and a salt of Compound 1 wherein the combination is present in an amount equivalent to about 49 wt. % of Compound 1.
10. The solid pharmaceutical formulation of claim 9 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.
11. The solid pharmaceutical formulation of claim 2 , consisting of
Compound 1 in an amount of about 49 wt. %;
lactose monohydrate in an amount of about 10-20 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 11-19 wt. %;
sodium starch glycolate in an amount of about 3-7 wt. %;
hydroxypropyl cellulose in an amount of about 1-10 wt. %;
magnesium stearate in an amount of about 0.5-5 wt. %; and
a coating composition in an amount of about 1-10 wt. %.
12. The solid pharmaceutical formulation of claim 2 , consisting of
a salt of Compound 1 in an amount equivalent to about 49 wt. % of Compound 1;
lactose monohydrate in an amount of about 10-20 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 11-19 wt. %;
sodium starch glycolate in an amount of about 3-7 wt. %;
hydroxypropyl cellulose in an amount of about 1-10 wt. %;
magnesium stearate in an amount of about 0.5-5 wt. %; and
a coating composition in an amount of about 1-10 wt. %.
13. The solid pharmaceutical formulation of claim 12 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.
14. The solid pharmaceutical formulation of claim 2 , consisting of
a combination of Compound 1 and a salt of Compound 1 wherein the combination is present in an amount equivalent to about 49 wt. % of Compound 1;
lactose monohydrate in an amount of about 10-20 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 11-19 wt. %;
sodium starch glycolate in an amount of about 3-7 wt. %;
hydroxypropyl cellulose in an amount of about 1-10 wt. %;
magnesium stearate in an amount of about 0.5-5 wt. %; and
a coating composition in an amount of about 1-10 wt. %.
15. The solid pharmaceutical formulation of claim 14 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.
16. The solid pharmaceutical formulation of claim 2 , consisting of
Compound 1 in an amount of about 49 wt. %;
lactose monohydrate in an amount of about 17 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 15 wt. %;
sodium starch glycolate in an amount of about 5 wt. %;
hydroxypropyl cellulose in an amount of about 4 wt. %;
magnesium stearate in an amount of about 2 wt. %; and
a coating composition in an amount of about 4 wt. %.
17. The solid pharmaceutical formulation of claim 2 , consisting of
a salt of Compound 1 in an amount equivalent to about 49 wt. % of Compound 1;
lactose monohydrate in an amount of about 17 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 15 wt. %;
sodium starch glycolate in an amount of about 5 wt. %;
hydroxypropyl cellulose in an amount of about 4 wt. %;
magnesium stearate in an amount of about 2 wt. %; and
a coating composition in an amount of about 4 wt. %.
18. The solid pharmaceutical formulation of claim 17 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.
19. The solid pharmaceutical formulation of claim 2 , consisting of
a combination of Compound 1 and a salt of Compound 1 wherein the combination is present in an amount equivalent to about 49 wt. % of Compound 1;
lactose monohydrate in an amount of about 17 wt. %;
low-substituted hydroxypropyl cellulose in an amount of about 15 wt. %;
sodium starch glycolate in an amount of about 5 wt. %;
hydroxypropyl cellulose in an amount of about 4 wt. %;
magnesium stearate in an amount of about 2 wt. %; and
a coating composition in an amount of about 4 wt. %.
20. The solid pharmaceutical formulation of claim 19 , wherein the salt of Compound 1 is a hydrobromide salt of Compound 1.