Divergent synthesis of a pochonin library targeting HSP90 and in vivo efficacy of an identified inhibitor

Abstract

(Chemical Equation Presented) Make a clean breast of it: The generation of a library of pochonin Dderivatives by a solid-phase approach has led to the discovery of pochoxime (see scheme), a potent inhibitor of the heat-shock protein 90, with over 100-fold improved incellular activity. Pochoxime was found to be effective in breast tumor xenografts, leading to a reduction in the tumor size. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.