GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2)

  • ACS Med Chem Lett. 2017 Jun 1;8(7):737-741. doi: 10.1021/acsmedchemlett.7b00132.
Terry D Crawford  1 ,  James E Audia  2 ,  Steve Bellon  2 ,  Daniel J Burdick  1 ,  Archana Bommi-Reddy  2 ,  Alexandre Côté  2 ,  Richard T Cummings  2 ,  Martin Duplessis  2 ,  E Megan Flynn  1 ,  Michael Hewitt  2 ,  Hon-Ren Huang  2 ,  Hariharan Jayaram  2 ,  Ying Jiang  3 ,  Shivangi Joshi  2 ,  James R Kiefer  1 ,  Jeremy Murray  1 ,  Christopher G Nasveschuk  2 ,  Arianne Neiss  2 ,  Eneida Pardo  2 ,  F Anthony Romero  1 ,  Peter Sandy  2 ,  Robert J Sims 3rd  2 ,  Yong Tang  2 ,  Alexander M Taylor  2 ,  Vickie Tsui  1 ,  Jian Wang  3 ,  Shumei Wang  1 ,  Yongyun Wang  3 ,  Zhaowu Xu  3 ,  Laura Zawadzke  2 ,  Xiaoqin Zhu  3 ,  Brian K Albrecht  2 ,  Steven R Magnuson  1 ,  Andrea G Cochran  1
Affiliations
  • 1. Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States.
  • 2. Constellation Pharmaceuticals, 215 First Street, Suite 200, Cambridge, Massachusetts 02142, United States.
  • 3. Wuxi Apptec Co., Ltd., 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, People's Republic of China.
PMID: 28740608 DOI: 10.1021/acsmedchemlett.7b00132
Abstract

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

Keywords
Bromodomain; CECR2; Epigenetics; Probe.
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