Discovery of benzisoxazoles as potent inhibitors of chaperone heat shock protein 90

Document Type

Article

Publication Date

2-14-2008

Abstract

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for activating many signaling proteins and is a promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show that these compounds bind in the ATP binding pocket interacting with the Asp93. Structure based optimization led to the identification of potent analogues, such as 13, with good biochemical profiles. © 2008 American Chemical Society.

Publication Title

Journal of Medicinal Chemistry

First Page Number

373

Last Page Number

375

DOI

10.1021/jm701385c

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