New use of specific cyklolignans

Abstract

The invention refers to the use of specific cyclolignans, wherein the carbon atoms in positions 9 and 9′ have cis configuration, for inhibition of the insulin-like growth factor-1 receptor. Said compounds can be used for treatment of IGF-1R dependent diseases, such as cancer, psoriasis, artherosclerosis and acromegaly. A preferred compound is picropodophyllin.

1 - 16 . (canceled) 
   
   
       17 . A composition, comprising:
 (a) a compound of formula I:   
     
       
         
         
             
             
         
       
     
     wherein
 each R 1  is, independently, OH or OCH 3 , 
 n is 0, 1 or 2, 
 R 2  is H or OH, 
 R 3  and R 4 , together, are an ether or a lactone, and 
 wherein the carbons in positions 9 and 9′ have a cis configuration and the 8-9 and 8′-9′ bonds are beta bonds, and
 (b) an anti-cancer drug. 
 
 
   
   
       18 . The composition of  claim 17 , wherein the compound of formula I is picropodophyllin. 
   
   
       19 . The composition of  claim 17 , wherein the compound of formula I is deoxypicropodophyllin. 
   
   
       20 . The composition of  claim 17 , wherein the anti-cancer drug is a cytostaticum. 
   
   
       21 . The composition of  claim 20 , wherein the cytostaticum is vincristin, taxol or etoposide. 
   
   
       22 . The composition of  claim 17 , wherein R 1  is OH. 
   
   
       23 . The composition of  claim 17 , wherein R 1  is OCH 3 . 
   
   
       24 . The composition of  claim 17 , wherein n is 0. 
   
   
       25 . The composition of  claim 17 , wherein n is 1. 
   
   
       26 . The composition of  claim 17 , wherein n is 2. 
   
   
       27 . The composition of  claim 17 , wherein R2 is H. 
   
   
       28 . The composition of  claim 17 , wherein R2 is OH. 
   
   
       29 . The composition of  claim 17 , wherein R3 and R4, together, are an ether. 
   
   
       30 . The composition of  claim 17 , wherein R3 and R4, together, are a lactone. 
   
   
       31 . The composition of  claim 17 , further comprising a physiologically acceptable carrier. 
   
   
       32 . A kit, comprising
 (a) a first container comprising a compound of formula I   
     
       
         
         
             
             
         
       
     
     wherein
 each R 1  is, independently, OH or OCH 3 , 
 n is 0, 1 or 2, 
 R 2  is H or OH, 
 R 3  and R 4 , together, are an ether or a lactone, and 
 wherein the carbons in positions 9 and 9′ have a cis configuration and the 8-9 and 8′-9′ bonds are beta bonds, and 
 (b) a second container comprising an anti-cancer drug. 
 
   
   
       33 . The kit of  claim 32 , wherein the anti-cancer drug is a cytostaticum. 
   
   
       34 . The kit of  claim 33 , wherein the cytostaticum is vincristin, taxol or etoposide. 
   
   
       35 . A method of treating cancer, comprising administering an effective amount of the composition of  claim 17  to a subject in need thereof. 
   
   
       36 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of the compound of formula I and the anti-cancer drug from the kit of  claim 32 . 
   
   
       37 . A method of treating a tumor, comprising administering an effective amount of the composition of  claim 17  to a subject in need thereof. 
   
   
       38 . A method of treating a tumor, comprising administering to a subject in need thereof an effective amount of the compound of formula I and the anti-cancer drug from the kit of  claim 32 .