Compositions and methods for the treatment of cancer

Abstract

The present invention relates to the use of specific compounds related to the indolocarbazole K252a, for the preparation of pharmaceutical compositions for the treatment of various forms of cancer.

1 . A method for treating an abnormal growth of cells in a subject in need of such treatment, comprising administering to said subject an effective amount of a compound of Formula 1, 2, 3 or 4: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . A method of inhibiting an activated kinase pathway in a subject in need of such treatment comprising administering to said subject an effective amount of a compound of Formula 1, 2, 3 or 4: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof. 
     
     
         5 . A method of treating cancer in a subject in need of such treatment comprising administering to said subject an effective amount of a compound of Formula 1, 2, 3 or 4: 
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof. 
     
     
         6 . The method of  claim 5 , wherein the cancer is selected from the group consisting of: breast cancers, colon cancers, gliomas, melanomas, prostate cancers, ovarian cancers, kidney cancers, bladder cancers, head and neck cancers, bone cancers, epidermal cancers, pancreatic cancers, esophageal cancers, stomach cancers, lung cancers, myeloid leukemias, thyroid follicular tumors, myelodysplastic syndrome, non-Hodgkin's lymphomas, and multiple myelomas. 
     
     
         7 . The method of  claim 5 , wherein the cancer is selected from the group consisting of lung cancer, colon cancer, brain cancer, melanoma, ovarian cancer, kidney cancer, prostate cancer and breast cancer. 
     
     
         8 . The method of  claim 5 , wherein said cancer is breast cancer, colon cancer, or glioma. 
     
     
         9 . The method of  claim 8 , wherein a the cancer is related to activation of a MAP protein kinase as a result of an oncogenic mutation in a gene encoding a cell surface receptor tyrosine kinase (RTK) or other upstream signaling protein. 
     
     
         10 . The method of  claim 9 , wherein said MAP protein kinase is extracellular signal regulated kinase-2 (ERK-2) and/or extracellular signal regulated kinase-1 (ERK-1), and wherein said other upstream signaling protein is a Raf or Ras protein. 
     
     
         11 - 19 . (canceled) 
     
     
         20 . A pharmaceutical composition comprising
 (1) a compound of Formula 1, 2, 3 or 4:   
       
         
           
           
               
               
           
         
       
       or pharmaceutically acceptable salts thereof;
 (2) at least one antihormonal agent; and 
 (3) a pharmaceutically acceptable carrier. 
 
     
     
         21 . The pharmaceutical composition of  claim 20 , further comprising at least one chemotherapeutic agent. 
     
     
         22 - 23 . (canceled)