Discovery of Benzisoxazoles as Potent Inhibitors of Chaperone Heat Shock Protein 90
Journal of Medicinal Chemistry2008Vol. 51(3), pp. 373–375
Citations Over TimeTop 10% of 2008 papers
Ariamala Gopalsamy, Mengxiao Shi, Jennifer M. Golas, Erik Vogan, Jaison Jacob, M. Catherine Johnson, Frederick Lee, Ramaswamy Nilakantan, Roseann Petersen, Kristin Svenson, Rajiv Chopra, May Tam, Yingxia Wen, John W. Ellingboe, Kim Arndt, Frank Boschelli
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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