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

  • J Med Chem. 2007 Mar 22;50(6):1280-7. doi: 10.1021/jm061381f.
Alex M Aronov  1 ,  Christopher Baker ,  Guy W Bemis ,  Jingrong Cao ,  Guanjing Chen ,  Pamella J Ford ,  Ursula A Germann ,  Jeremy Green ,  Michael R Hale ,  Marc Jacobs ,  James W Janetka ,  Francois Maltais ,  Gabriel Martinez-Botella ,  Mark N Namchuk ,  Judy Straub ,  Qing Tang ,  Xiaoling Xie
Affiliations
  • 1. Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, Massachusetts 02139-4242, USA. [email protected]
PMID: 17300186 DOI: 10.1021/jm061381f
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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