Identification of a buried pocket for potent and selective inhibition of Chk1: prediction and verification

…, LM Fisher, G Francis, R Howes, P Kierstan…

Index: Foloppe, Nicolas; Fisher, Lisa M.; Francis, Geraint; Howes, Rob; Kierstan, Peter; Potter, Andrew Bioorganic and Medicinal Chemistry, 2006 , vol. 14, # 6 p. 1792 - 1804

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Citation Number: 47

Abstract

Inhibition of the Chk1 kinase by small molecules binding to its active site is a strategy of great therapeutic interest for oncology. We report how computational modelling predicted the binding mode of ligands of special interest to the Chk1 ATP site, for representatives of an indazole series and debromohymenialdisine. These binding modes were subsequently confirmed by X-ray crystallography. The binding mode of a potent indazole derivative ...