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

  • J Med Chem. 2008 Feb 14;51(3):373-5. doi: 10.1021/jm701385c.
Ariamala Gopalsamy  1 ,  Mengxiao Shi ,  Jennifer Golas ,  Erik Vogan ,  Jaison Jacob ,  Mark Johnson ,  Frederick Lee ,  Ramaswamy Nilakantan ,  Roseann Petersen ,  Kristin Svenson ,  Rajiv Chopra ,  May S Tam ,  Yingxia Wen ,  John Ellingboe ,  Kim Arndt ,  Frank Boschelli
Affiliations
  • 1. Chemical and Screening Sciences, Wyeth Research, Pearl River, NY 10965, USA. [email protected]
PMID: 18197612 DOI: 10.1021/jm701385c
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.

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