Michael Sherman - Newton MA,
Stuart K Calderwood - Chestnut Hill MA,
Nava Zaarur - Brookline MA,
TRUSTEES OF BOSTON UNIVERSITY - Boston MA
514 34, 514283, 514450, 514183, 514 64, 514267, 514294
The present invention is based on the discovery that inactivation of the heat shock response in cancer cells significantly enhances their sensitivity to proteasome and Hsp90 inhibitors. The inventors have discovered novel compounds which exhibit low toxicity, inhibit the heat shock protein response and sensitize cancer cells to anti-cancer therapies. In general, the heat shock protein inhibitors of the present invention share a common structure, namely a 2H-benzo[a]quinolizine tricyclic ring. Also encompassed are methods for a high throughput screen to identify heat shock inhibitors that sensitize cancer cells to anti-cancer therapies.