Tautomycetin and tautomycetin analog biosynthesis
The present invention relates to tautomycetin (TTN) and analogs thereof. Also provided are methods of using TTN and analogs thereof in the treatment of various diseases relating to SHP2 function.
1. A method of treating a SHP2-related cancer in a subject comprising contacting a SHP2-related cancer cell with an analog of tautomycetin thereof, wherein said analog has the structure:
wherein X═O, OH or H, and R═(CH) 2 COOH or CH(OH)CH 2 COOH.
2. The method of claim 1 , wherein X is ═OH.
3. The method of claim 1 , wherein X is ═O.
4. The method of claim 1 , wherein said compound is:
5. The method of claim 1 , wherein said compound is:
6. The method of claim 1 , wherein said compound is:
7. The method of claim 1 , wherein said compound is:
8. The method of claim 1 , wherein said compound is:
9. The method of claim 1 , wherein X is H.
10. The method of claim 1 , wherein said SHP2-related cancer is not colorectal cancer.
11. The method of claim 1 , wherein said SHP2-related cancer is not leukemia.
12. The method of claim 1 , further comprising contacting said cancer cell with a second anti-cancer therapy.
13. The method of claim 12 , wherein said second anti-cancer therapy is selected from radiotherapy, chemotherapy, immunotherapy, chemotherapy and gene therapy.
14. The method of claim 1 , wherein said cancer is multi-drug-resistant, recurrent or metastatic.
15. The method of claim 1 , wherein said subject is a human.
16. The method of claim 1 , further comprising assessing a cancer cell from said subject for a mutation in SHP2.
17. A method of treating Noonan syndrome comprising administering to a subject an analog of tautomycetin thereof, wherein said analog has the structure:
wherein X═O, OH or H, and R═(CH) 2 COOH or CH(OH)CH 2 COOH.
18. The method of claim 17 , wherein said subject is treated with tautomycetin.
19. The method of claim 17 , further comprising assessing a cancer cell from said subject for a mutation in SHP2.
20. A method of treating Leopard syndrome comprising administering to a subject an analog of tautomycetin thereof, wherein said analog has the structure:
wherein X═O, OH or H, and R═(CH) 2 COOH or CH(OH)CH 2 COOH.
21. The method of claim 20 , wherein said subject is treated with tautonycetin.
22. The method of claim 20 , further comprising assessing a cancer cell from said subject for a mutation in SHP2.
23. The method of claim 17 , wherein X is H.
24. The method of claim 17 , wherein X is —OH.
25. The method of claim 17 , wherein X is ═O.
26. The method of claim 17 , wherein said compound is:
27. The method of claim 17 , wherein said compound is:
28. The method of claim 17 , wherein said compound is:
29. The method of claim 17 , wherein said compound is:
30. The method of claim 17 , wherein said compound is:
31. The method of claim 20 , wherein X is H.
32. The method of claim 20 , wherein X is —OH.
33. The method of claim 20 , wherein X is ═O.
34. The method of claim 20 , wherein said compound is:
35. The method of claim 20 , wherein said compound is:
36. The method of claim 20 , wherein said compound is:
37. The method of claim 20 , wherein said compound is:
38. The method of claim 20 , wherein said compound is: