| Literature DB >> 19969456 |
Andrew J Potter1, Stuart Ray, Louisa Gueritz, Claire L Nunns, Christopher J Bryant, Simon F Scrace, Natalia Matassova, Lisa Baker, Pawel Dokurno, David A Robinson, Allan E Surgenor, Ben Davis, James B Murray, Christine M Richardson, Jonathan D Moore.
Abstract
The peptidyl prolyl cis/trans isomerase Pin1 is a promising molecular target for anti-cancer therapeutics. Here we report the structure-guided evolution of an indole 2-carboxylic acid fragment hit into a series of alpha-benzimidazolyl-substituted amino acids. Examples inhibited Pin1 activity with IC(50) <100nM, but were inactive on cells. Replacement of the benzimidazole ring with a naphthyl group resulted in a 10-50-fold loss in ligand potency, but these examples downregulated biomarkers of Pin1 activity and blocked proliferation of PC3 cells. Copyright 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 19969456 DOI： 10.1016/j.bmcl.2009.11.090
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823