Pfizer Global Research and Development, La Jolla Laboratories, 10770, Science Center Dr., San Diego, CA 92121, USA. peipei.kung@pfizer.com
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.