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12:00 AM
 | 
Mar 21, 2011
 |  BioCentury  |  Product Development

Safe to move forward vs. Hsp90

Ganetespib looking safe; Synta advances Hsp90 inhibitor for lung cancer

Based on recently reported Phase II data, Synta Pharmaceuticals Corp. thinks it has the first Hsp90 inhibitor to have both meaningful cancer activity and a clean safety profile. It plans to start a Phase IIb/III trial of ganetespib for lung cancer next quarter.

Heat shock protein 90 (Hsp90) is a molecular chaperone that helps fold, stabilize and activate various growth factors and kinases that promote tumor growth, survival and metastasis. Its central role in a wide variety of oncogenic processes has made it a popular target for small molecule drug developers.

But several of the Hsp90 inhibitors that have reached the clinic have been shelved due to unacceptable toxicities or insufficient activity.

"The first-generation compounds were derivatives of an antibiotic called geldanamycin that was actually identified as an Hsp90 inhibitor serendipitously. But it turned out to be a fairly lousy drug because it was not a potent inhibitor and caused some serious liver toxicity," said President and CEO Safi Bahcall.

The most advanced of the first-generation inhibitors was tanespimycin, a geldanamycin analog Kosan Biosciences Inc. had moved into Phase III testing for multiple melanoma (MM). Bristol-Myers...

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