Bromodomain inhibitor
Described herein is the bromodomain inhibitor 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, including crystalline forms, amorphous forms, solvates, and hydrates thereof, as well as pharmaceutical compositions that include this bromodomain inhibitor. In some embodiments, the pharmaceutical composition comprises 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one that has been processed by micronization or spray dried dispersion. In some embodiments, the pharmaceutical composition further comprises at least one polymer. In some embodiments, the pharmaceutical composition comprises a solid polymer matrix comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one and at least one polymer. Pharmaceutical compositions comprising 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one are useful for the treatment of cancer or neoplastic disease.
1. A method for treating cancer or other neoplastic disease, which is selected from the group consisting of Burkitts lymphoma, acute myeloid leukemia (AML), glioblastoma (GBM), and any combination thereof, in a subject in need of such treatment comprising administering to the subject a pharmaceutical composition comprising a spray dried dispersion or a micronized form of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one.
2. The method of claim 1 , wherein the pharmaceutical composition comprises at least one solid matrix polymer.
3. The method of claim 2 , wherein the pharmaceutical composition comprises a solid polymer matrix comprising:
(a) amorphous 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one, and
(b) a polymer selected from polyvinylpyrrolidone, hydroxypropyl methylcellulose, or hydroxypropylmethylcellulose-acetate-succinate;
wherein the solid polymer matrix is a spray dried dispersion.
4. The method of claim 1 , wherein the 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one exhibits XRPD reflection peaks at 7.8, 9.0, 15.7, 18.0, 21.1, 22.0, 23.6 and 24.5 2-theta (2θ).
5. The method of claim 2 , wherein the ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one to solid matrix polymer is from about 1:1 to about 1:9.
6. The method of claim 2 , wherein the ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one to solid matrix polymer is about 1:1, about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, or about 1:9.
7. The method of claim 2 , wherein the polymer is hydroxypropyl methylcellulose and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:3.
8. The method of claim 2 , wherein the polymer is hydroxypropyl methylcellulose and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:1.
9. The method of claim 2 , wherein the polymer is polyvinylpyrrolidone and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:3.
10. The method of claim 2 , wherein the polymer is polyvinylpyrrolidone and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:1.
11. The method of claim 2 , wherein the polymer is hydroxypropylmethylcellulose acetate succinate and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:3.
12. The method of claim 2 , wherein the polymer is hydroxy-propylmethylcellulose acetate succinate and is present in a ratio of 4-[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]-2-methylisoquinolin-1-one:polymer of about 1:1.
13. The method of claim 1 , wherein the cancer is Burkitts lymphoma.
14. The method of claim 1 , wherein the cancer is acute myeloid leukemia (AML).
15. The method of claim 1 , wherein the cancer is glioblastoma (GBM).