Literature DB >> 28740608

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

Terry D Crawford1, James E Audia2, Steve Bellon2, Daniel J Burdick1, Archana Bommi-Reddy2, Alexandre Côté2, Richard T Cummings2, Martin Duplessis2, E Megan Flynn1, Michael Hewitt2, Hon-Ren Huang2, Hariharan Jayaram2, Ying Jiang3, Shivangi Joshi2, James R Kiefer1, Jeremy Murray1, Christopher G Nasveschuk2, Arianne Neiss2, Eneida Pardo2, F Anthony Romero1, Peter Sandy2, Robert J Sims2, Yong Tang2, Alexander M Taylor2, Vickie Tsui1, Jian Wang3, Shumei Wang1, Yongyun Wang3, Zhaowu Xu3, Laura Zawadzke2, Xiaoqin Zhu3, Brian K Albrecht2, Steven R Magnuson1, Andrea G Cochran1.   

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.

Entities:  

Keywords:  Bromodomain; CECR2; Epigenetics; Probe

Year:  2017        PMID： 28740608      PMCID： PMC5512139          DOI： 10.1021/acsmedchemlett.7b00132

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  18 in total

1.  The bromodomain: a chromatin-targeting module?

Authors:  F Winston; C D Allis
Journal:  Nat Struct Biol       Date:  1999-07

2.  The bromodomain: a conserved sequence found in human, Drosophila and yeast proteins.

Authors:  S R Haynes; C Dollard; F Winston; S Beck; J Trowsdale; I B Dawid
Journal:  Nucleic Acids Res       Date:  1992-05-25       Impact factor: 16.971

3.  Regulatory T Cell Modulation by CBP/EP300 Bromodomain Inhibition.

Authors:  Srimoyee Ghosh; Alexander Taylor; Melissa Chin; Hon-Ren Huang; Andrew R Conery; Jennifer A Mertz; Andres Salmeron; Pranal J Dakle; Deanna Mele; Alexandre Cote; Hari Jayaram; Jeremy W Setser; Florence Poy; Georgia Hatzivassiliou; Denise DeAlmeida-Nagata; Peter Sandy; Charlie Hatton; F Anthony Romero; Eugene Chiang; Thornik Reimer; Terry Crawford; Eneida Pardo; Venita G Watson; Vickie Tsui; Andrea G Cochran; Laura Zawadzke; Jean-Christophe Harmange; James E Audia; Barbara M Bryant; Richard T Cummings; Steven R Magnuson; Jane L Grogan; Steve F Bellon; Brian K Albrecht; Robert J Sims; Jose M Lora
Journal:  J Biol Chem       Date:  2016-04-07       Impact factor: 5.157

Review 4.  Small molecule inhibitors of bromodomain-acetyl-lysine interactions.

Authors:  Michael Brand; Angelina R Measures; Angelina M Measures; Brian G Wilson; Wilian A Cortopassi; Rikki Alexander; Matthias Höss; David S Hewings; Timothy P C Rooney; Robert S Paton; Stuart J Conway
Journal:  ACS Chem Biol       Date:  2015-01-16       Impact factor: 5.100

5.  Chemical studies of histone acetylation. The occurrence of epsilon-N-acetyllysine in the f2a1 histone.

Authors:  E L Gershey; G Vidali; V G Allfrey
Journal:  J Biol Chem       Date:  1968-10-10       Impact factor: 5.157

6.  Structure and ligand of a histone acetyltransferase bromodomain.

Authors:  C Dhalluin; J E Carlson; L Zeng; C He; A K Aggarwal; M M Zhou
Journal:  Nature       Date:  1999-06-03       Impact factor: 49.962

7.  CECR2 is involved in spermatogenesis and forms a complex with SNF2H in the testis.

Authors:  Peter J Thompson; Kacie A Norton; Farshad H Niri; Christine E Dawe; Heather E McDermid
Journal:  J Mol Biol       Date:  2011-12-02       Impact factor: 5.469

8.  CECR2, a protein involved in neurulation, forms a novel chromatin remodeling complex with SNF2L.

Authors:  Graham S Banting; Orr Barak; Tanya M Ames; Amanda C Burnham; Melanie D Kardel; Neil S Cooch; Courtney E Davidson; Roseline Godbout; Heather E McDermid; Ramin Shiekhattar
Journal:  Hum Mol Genet       Date:  2005-01-07       Impact factor: 6.150

Review 9.  The role of human bromodomains in chromatin biology and gene transcription.

Authors:  Roberto Sanchez; Ming-Ming Zhou
Journal:  Curr Opin Drug Discov Devel       Date:  2009-09

10.  Diving into the Water: Inducible Binding Conformations for BRD4, TAF1(2), BRD9, and CECR2 Bromodomains.

Authors:  Terry D Crawford; Vickie Tsui; E Megan Flynn; Shumei Wang; Alexander M Taylor; Alexandre Côté; James E Audia; Maureen H Beresini; Daniel J Burdick; Richard Cummings; Les A Dakin; Martin Duplessis; Andrew C Good; Michael C Hewitt; Hon-Ren Huang; Hariharan Jayaram; James R Kiefer; Ying Jiang; Jeremy Murray; Christopher G Nasveschuk; Eneida Pardo; Florence Poy; F Anthony Romero; Yong Tang; Jian Wang; Zhaowu Xu; Laura E Zawadzke; Xiaoyu Zhu; Brian K Albrecht; Steven R Magnuson; Steve Bellon; Andrea G Cochran
Journal:  J Med Chem       Date:  2016-05-31       Impact factor: 7.446
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  3 in total

1.  Large-scale analysis of water stability in bromodomain binding pockets with grand canonical Monte Carlo.

Authors:  Matteo Aldeghi; Gregory A Ross; Michael J Bodkin; Jonathan W Essex; Stefan Knapp; Philip C Biggin
Journal:  Commun Chem       Date:  2018-04-05

2.  CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression.

Authors:  Meiling Zhang; Zongzhi Z Liu; Keisuke Aoshima; Wesley L Cai; Hongyin Sun; Tianrui Xu; Yangyi Zhang; Yongyan An; Jocelyn F Chen; Lok Hei Chan; Asako Aoshima; Sabine M Lang; Zhenwei Tang; Xuanlin Che; Yao Li; Sara J Rutter; Veerle Bossuyt; Xiang Chen; Jon S Morrow; Lajos Pusztai; David L Rimm; Mingzhu Yin; Qin Yan
Journal:  Sci Transl Med       Date:  2022-02-02       Impact factor: 19.319

3.  A chemical toolbox for the study of bromodomains and epigenetic signaling.

Authors:  Qin Wu; David Heidenreich; Stanley Zhou; Suzanne Ackloo; Andreas Krämer; Kiran Nakka; Evelyne Lima-Fernandes; Genevieve Deblois; Shili Duan; Ravi N Vellanki; Fengling Li; Masoud Vedadi; Jeffrey Dilworth; Mathieu Lupien; Paul E Brennan; Cheryl H Arrowsmith; Susanne Müller; Oleg Fedorov; Panagis Filippakopoulos; Stefan Knapp
Journal:  Nat Commun       Date:  2019-04-23       Impact factor: 14.919
  3 in total

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