Small molecule antagonists of bcl2 family proteins

Abstract

The present invention relates to naturally occurring and chemically synthesized small molecule antagonists of Bcl-2 family proteins. In particular, the present invention provides gossypol compounds (e.g., isomers, enantiomers, racemic compounds, metabolites, derivatives, pharmaceutically acceptable salts, in combination with acids or bases, and the like) and methods of using these compounds as antagonists of the anti-apoptotic effects of Bcl-2 family member proteins (e.g., Bcl-2, Bcl-X L, and the like). The present invention also provides compositions comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents). The present invention also provides methods for treating diseases and pathologies (e.g., neoplastic diseases) comprising administering a composition comprising gossypol compounds and optionally one or more additional therapeutic agents (e.g., anticancer/chemotherapeutic agents) and/or techniques (e.g., radiation therapies, surgical interventions, and the like) to a subject or in vitro cells, tissues, and organs.

1 .- 51 . (canceled) 
     
     
         52 . A pharmaceutical composition comprising a gossypol compound and prednisone. 
     
     
         53 . The pharmaceutical composition of  claim 52  further comprising a pharmaceutically acceptable carrier. 
     
     
         52 . The pharmaceutical composition of  claim 52  formulated as a tablet, pill, or capsule for oral ingestion by a subject in need thereof. 
     
     
         55 . A kit comprising the pharmaceutical composition of  claim 52  and instructions for administering said pharmaceutical composition to a subject in need thereof. 
     
     
         56 . The kit of  claim 55  further comprising one or more anticancer agents. 
     
     
         57 . The kit of  claim 56  further comprising instructions for administering said one or more anticancer agents to said subject. 
     
     
         58 . The kit of  claim 56 , wherein said anticancer agent is selected from the group consisting of docetaxel and paclitaxel. 
     
     
         59 . The kit of  claim 58  wherein said anticancer agent is docetaxel. 
     
     
         60 . The pharmaceutical composition of any one of  claims 52 - 54  wherein said gossypol compound is (−)-gossypol. 
     
     
         61 . The kit of any one of  claims 55 - 59  wherein said pharmaceutical composition comprises (−)-gossypol.