Literature DB >> 24900801

Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.

Ramzi F Sweis1, Marina Pliushchev1, Peter J Brown2, Jun Guo1, Fengling Li2, David Maag1, Andrew M Petros1, Nirupama B Soni1, Chris Tse1, Masoud Vedadi2, Michael R Michaelides1, Gary G Chiang1, William N Pappano1.   

Abstract

G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.

Entities:  

Keywords:  A-366; G9a; epigenetics; methylation; methyltransferase

Year:  2014        PMID： 24900801      PMCID： PMC4027767          DOI： 10.1021/ml400496h

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


  20 in total

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Authors:  Robert Schneider; Andrew J Bannister; Tony Kouzarides
Journal:  Trends Biochem Sci       Date:  2002-08       Impact factor: 13.807

Review 2.  Epigenetic modifications and human disease.

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Journal:  Nat Biotechnol       Date:  2010-10       Impact factor: 54.908

3.  Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase.

Authors:  Stefan Kubicek; Roderick J O'Sullivan; E Michael August; Eugene R Hickey; Qiang Zhang; Miguel L Teodoro; Stephen Rea; Karl Mechtler; Jennifer A Kowalski; Carol Ann Homon; Terence A Kelly; Thomas Jenuwein
Journal:  Mol Cell       Date:  2007-02-09       Impact factor: 17.970

Review 4.  Covalent histone modifications--miswritten, misinterpreted and mis-erased in human cancers.

Authors:  Ping Chi; C David Allis; Gang Greg Wang
Journal:  Nat Rev Cancer       Date:  2010-07       Impact factor: 60.716

5.  A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells.

Authors:  Masoud Vedadi; Dalia Barsyte-Lovejoy; Feng Liu; Sylvie Rival-Gervier; Abdellah Allali-Hassani; Viviane Labrie; Tim J Wigle; Peter A Dimaggio; Gregory A Wasney; Alena Siarheyeva; Aiping Dong; Wolfram Tempel; Sun-Chong Wang; Xin Chen; Irene Chau; Thomas J Mangano; Xi-Ping Huang; Catherine D Simpson; Samantha G Pattenden; Jacqueline L Norris; Dmitri B Kireev; Ashutosh Tripathy; Aled Edwards; Bryan L Roth; William P Janzen; Benjamin A Garcia; Arturas Petronis; James Ellis; Peter J Brown; Stephen V Frye; Cheryl H Arrowsmith; Jian Jin
Journal:  Nat Chem Biol       Date:  2011-07-10       Impact factor: 15.040

6.  Identification of a specific inhibitor of the histone methyltransferase SU(VAR)3-9.

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Journal:  Nat Chem Biol       Date:  2005-07-17       Impact factor: 15.040

Review 7.  The epigenomics of cancer.

Authors:  Peter A Jones; Stephen B Baylin
Journal:  Cell       Date:  2007-02-23       Impact factor: 41.582

8.  The structure-activity relationships of L3MBTL3 inhibitors: flexibility of the dimer interface.

Authors:  Michelle A Camerino; Nan Zhong; Aiping Dong; Bradley M Dickson; Lindsey I James; Brandi M Baughman; Jacqueline L Norris; Dmitri B Kireev; William P Janzen; Cheryl H Arrowsmith; Stephen V Frye
Journal:  Medchemcomm       Date:  2013-11       Impact factor: 3.597

9.  Discovery of an in vivo chemical probe of the lysine methyltransferases G9a and GLP.

Authors:  Feng Liu; Dalia Barsyte-Lovejoy; Fengling Li; Yan Xiong; Victoria Korboukh; Xi-Ping Huang; Abdellah Allali-Hassani; William P Janzen; Bryan L Roth; Stephen V Frye; Cheryl H Arrowsmith; Peter J Brown; Masoud Vedadi; Jian Jin
Journal:  J Med Chem       Date:  2013-10-31       Impact factor: 7.446

10.  Downregulation of histone H3 lysine 9 methyltransferase G9a induces centrosome disruption and chromosome instability in cancer cells.

Authors:  Yutaka Kondo; Lanlan Shen; Saira Ahmed; Yanis Boumber; Yoshitaka Sekido; Bassem R Haddad; Jean-Pierre J Issa
Journal:  PLoS One       Date:  2008-04-30       Impact factor: 3.240
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  54 in total

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Authors:  Frann Antignano; Colby Zaph
Journal:  Immunol Cell Biol       Date:  2015-01-13       Impact factor: 5.126

Review 2.  Inhibitors of Protein Methyltransferases and Demethylases.

Authors:  H Ümit Kaniskan; Michael L Martini; Jian Jin
Journal:  Chem Rev       Date:  2017-03-24       Impact factor: 60.622

3.  Structure-activity relationship studies of G9a-like protein (GLP) inhibitors.

Authors:  Yan Xiong; Fengling Li; Nicolas Babault; Hong Wu; Aiping Dong; Hong Zeng; Xin Chen; Cheryl H Arrowsmith; Peter J Brown; Jing Liu; Masoud Vedadi; Jian Jin
Journal:  Bioorg Med Chem       Date:  2017-06-19       Impact factor: 3.641

4.  Turning a Substrate Peptide into a Potent Inhibitor for the Histone Methyltransferase SETD8.

Authors:  Russell A Judge; Haizhong Zhu; Anup K Upadhyay; Pierre M Bodelle; Charles W Hutchins; Maricel Torrent; Violeta L Marin; Wenyu Yu; Masoud Vedadi; Fengling Li; Peter J Brown; William N Pappano; Chaohong Sun; Andrew M Petros
Journal:  ACS Med Chem Lett       Date:  2016-10-11       Impact factor: 4.345

5.  Developing Spindlin1 small-molecule inhibitors by using protein microarrays.

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Journal:  Nat Chem Biol       Date:  2017-05-15       Impact factor: 15.040

Review 6.  Nonhistone Lysine Methylation in the Regulation of Cancer Pathways.

Authors:  Scott M Carlson; Or Gozani
Journal:  Cold Spring Harb Perspect Med       Date:  2016-11-01       Impact factor: 6.915

7.  The H3K9 dimethyltransferases EHMT1/2 protect against pathological cardiac hypertrophy.

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Review 8.  Marked for death: targeting epigenetic changes in cancer.

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9.  Discovery of Potent and Selective Inhibitors for G9a-Like Protein (GLP) Lysine Methyltransferase.

Authors:  Yan Xiong; Fengling Li; Nicolas Babault; Aiping Dong; Hong Zeng; Hong Wu; Xin Chen; Cheryl H Arrowsmith; Peter J Brown; Jing Liu; Masoud Vedadi; Jian Jin
Journal:  J Med Chem       Date:  2017-02-14       Impact factor: 7.446

10.  S-adenosyl methionine is necessary for inhibition of the methyltransferase G9a by the lysine 9 to methionine mutation on histone H3.

Authors:  Hariharan Jayaram; Dominik Hoelper; Siddhant U Jain; Nico Cantone; Stefan M Lundgren; Florence Poy; C David Allis; Richard Cummings; Steven Bellon; Peter W Lewis
Journal:  Proc Natl Acad Sci U S A       Date:  2016-05-16       Impact factor: 11.205
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