Benzoquinone ansamycins

Abstract

The invention relates to benzoquinone ansamycin analogs useful for the treatment of cancer and other diseases or conditions characterized by undesired cellular proliferation or hyperproliferation. Therapies involving the administration of such benzoquinone ansamycin analogs, optionally in combination with an inhibitor of an HSP90 client protein, are useful to treat cancer and non-cancerous disease conditions.

1 . A method for treatment of a disease or condition characterized by undesired cellular proliferation or hyperproliferation in a subject suffering therefrom, comprising the steps of:
 (a) administering to said subject a substantially sub-toxic dose of an Hsp90 client protein inhibitor, wherein the Hsp90 client protein inhibitor is a microtubule stabilizing agent;   (b) waiting a period of time sufficient to allow development of a substantially efficacious response; and   (c) administering to said subject a synergistic dose of a benzoquinone ansamycin.   
     
     
         2 . The method of  claim 1  wherein the benzoquinone ansamycin is selected from the group consisting of 17-allylamino-17 desmethoxy-geldanamycin, and 17-(2-(dimethylamino)ethylamino-17-desmethoxygeldanamycin. 
     
     
         3 . The method of  claim 1 , wherein the disease is breast cancer. 
     
     
         4 . A method for treatment of a disease or condition characterized by undesired cellular proliferation or hyperproliferation in a subject suffering therefrom, comprising the steps of:
 (a) administering to said subject a synergistic dose of a benzoquinone ansamycin;   (b) waiting a period of time sufficient to allow development of a substantially efficacious response; and   (c) administering to said subject a sub-toxic dose of an Hsp90 client protein inhibitor, wherein the Hsp90 client protein inhibitor is a microtubule stabilizing agent.   
     
     
         5 . The method of  claim 4  wherein the microtubule stabilizing agent is selected from the group consisting of paclitaxel, an epothilone, discodermolide, and laulimalide. 
     
     
         6 . The method of  claim 4  wherein the benzoquinone ansamycin is selected from the group consisting of 17-allylamino-17 desmethoxy-geldanamycin, and 17 (2 (dimethylamino)ethylamino-17-desmethoxygeldanamycin. 
     
     
         7 . The method of  claim 4 , wherein the disease is breast cancer.