Use of specific cyklolignans
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. A method of treating neuroblastoma, glioma, myeloma, lymphoma, gastrointestinal tumors, gynecological cancers or lung cancer, the cells of which express the insulin-like growth factor-1 receptor, comprising administering to a mammal an effective amount of a compound represented by the formula I:
wherein
R 1 is OCH 3 ,
n is 0, 1 or 2,
R 2 is H or OH, and
R 3 and R 4 together are an ether or a lactone, and
wherein the carbon atoms at positions 9 and 9′ have cis configuration,
with the proviso that when n is 2 and R 2 is H, R 3 and R 4 together are an ether.
2. The method of claim 1 , wherein the compound inhibits the insulin-like growth factor-1 receptor without inhibiting the insulin receptor.
3. The method of claim 1 , wherein the compound is administered for the treatment of neuroblastoma.
4. The method of claim 1 , wherein the compound is administered for the treatment of glioblastoma.
5. The method of claim 1 , wherein the compound is administered for the treatment of myeloma.
6. The method of claim 1 , wherein the compound is administered for the treatment of lymphoma.
7. The method of claim 1 , wherein the compound is administered for the treatment of gastric cancer.
8. The method of claim 1 , wherein the compound is administered for the treatment of colonic cancer.
9. The method of claim 1 , wherein the compound is administered for the treatment of pancreatic carcinoma.
10. The method of claim 1 , wherein the compound is administered for the treatment of ovarial cancer.
11. The method of claim 1 , wherein the compound is administered for the treatment of endometric carcinoma.
12. The method of claim 1 , wherein the compound is administered for the treatment of lung cancer.
13. The method of claim 1 , wherein the compound is picropodophyllin.
14. The method of claim 1 , wherein the compound represented by formula I is administered in the form of a composition which also comprises a physiologically acceptable diluent.
15. The method of claim 1 , wherein the compound is administered in an amount effective for keeping the plasma level of the compound at a concentration of 0.05-5.0 μM.
16. The method of claim 1 , wherein the compound of formula I is administered with a cytostaticum.