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J Med Chem. 2007 Mar 22;50(6):1280-7. Epub 2007 Feb 15.

Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.

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  • 1Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, Massachusetts 02139-4242, USA. alex_aronov@vrtx.com

Abstract

The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

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