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

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

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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