Compositions of cyclin dependent kinase 7 (CDK7) inhibitor
The present invention provides, in part, compositions comprising an inhibitor of cyclin-dependent kinase 7 (CDK7) and sulfobutyl ether-β-cyclodextrin. Also provided are methods of using a disclosed composition for treating proliferative diseases. The present invention also provides methods of making disclosed compositions.
1. A pharmaceutical composition comprising SBEβCD and N-((1S,3R)-3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino)-1-methylcyclohexyl)-5-((E)-4-(dimethylamino)but-2-enamido)picolinamide (Compound 1) or a pharmaceutically acceptable salt thereof.
2. The pharmaceutical composition of claim 1 , wherein the composition further comprises one or more pharmaceutically acceptable excipients, a surfactant, or an acid.
3. The pharmaceutical composition of claim 2 , wherein the surfactant is Tween 80 and the acid is hydrochloric acid.
4. The pharmaceutical composition of claim 1 , wherein the SBEβCD has an average degree of substitution of about 6 to about 7.
5. The pharmaceutical composition of claim 1 , wherein the composition is a particulate composition or an aqueous solution.
6. The pharmaceutical composition of claim 5 , wherein the weight-to-weight ratio of the SBEβCD and Compound 1 or the pharmaceutically acceptable salt thereof is from about 30:1 to about 50:1.
7. The pharmaceutical composition of claim 5 , wherein the composition is particulate and comprises from about 1% to about 3% by weight Compound 1, or the pharmaceutically acceptable salt thereof, or wherein the composition is an aqueous solution comprising 1 mg/mL to about 10 mg/mL Compound 1 or the pharmaceutically acceptable salt thereof.
8. The pharmaceutical composition of claim 5 , wherein the composition is particulate and further comprises from about 1% to about 3% by weight surfactant.
9. The pharmaceutical composition of claim 1 , wherein the composition comprises a therapeutically effective amount of Compound 1 or the pharmaceutically acceptable salt thereof.
10. The pharmaceutical composition of claim 5 , wherein the particulate is a lyophilizate.
11. The pharmaceutical composition of claim 5 , wherein the composition is an aqueous solution having a pH from about 3.0 to about 4.0.
12. The pharmaceutical composition of claim 5 , wherein the composition further comprises less than 100 ppm of a phosphate.
13. The pharmaceutical composition of claim 5 , wherein the composition further comprises:
less than 20 ppm of a sulfoalkylating agent;
less than 0.5% by weight of an underivatized cyclodextrin;
less than 1% by weight of an alkali metal halide salt; or
less than 0.25% by weight of a hydrolyzed sulfoalkylating agent.
14. The pharmaceutical composition of claim 1 , wherein the composition is formulated for parenteral administration.
15. A method of preparing the pharmaceutical composition of claim 5 , wherein the composition is a particulate and the method comprises:
(a) dissolving SBEβCD, N-((1S,3R)-3-(5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino) -1-methylcyclohexyl)-5-((E)-4-(dimethylamino)but-2-enamido)picolinamide (Compound 1) or a pharmaceutically salt thereof, and optionally one or more pharmaceutically acceptable excipients in water; and
(b) lyophilizing the solution.