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Merck
CN
  • Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution.

Discovery of cell-active phenyl-imidazole Pin1 inhibitors by structure-guided fragment evolution.

Bioorganic & medicinal chemistry letters (2010-10-12)
Andrew Potter, Victoria Oldfield, Claire Nunns, Christophe Fromont, Stuart Ray, Christopher J Northfield, Christopher J Bryant, Simon F Scrace, David Robinson, Natalia Matossova, Lisa Baker, Pawel Dokurno, Allan E Surgenor, Ben Davis, Christine M Richardson, James B Murray, Jonathan D Moore
PMID20932746
摘要

Pin1 is an emerging oncology target strongly implicated in Ras and ErbB2-mediated tumourigenesis. Pin1 isomerizes bonds linking phospho-serine/threonine moieties to proline enabling it to play a key role in proline-directed kinase signalling. Here we report a novel series of Pin1 inhibitors based on a phenyl imidazole acid core that contains sub-μM inhibitors. Compounds have been identified that block prostate cancer cell growth under conditions where Pin1 is essential.