Pei-Pei Kung,
Lee Funk,
Jerry Meng,
Michael Collins,
Joe Zhongxiang Zhou,
M Catherine Johnson,
Anne Ekker,
Jeff Wang,
Pramod Mehta,
Min-Jean Yin,
Caroline Rodgers, Jay F Davies,
Eileen Bayman,
Tod Smeal,
Karen A Maegley,
Michael R Gehring
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ABSTRACT: Information from X-ray crystal structures were used to optimize the potency of a HTS hit in a Hsp90 competitive binding assay. A class of novel and potent small molecule Hsp90 inhibitors were thereby identified. Enantio-pure compounds 31 and 33 were potent in PGA-based competitive binding assay and inhibited proliferation of various human cancer cell lines in vitro, with IC(50) values averaging 20 nM.
Bioorganic & medicinal chemistry letters 10/2008; 18(23):6273-8. · 2.65 Impact Factor