Literature DB >> 26101576

Discovery of A-893, A New Cell-Active Benzoxazinone Inhibitor of Lysine Methyltransferase SMYD2.

Ramzi F Sweis1, Zhi Wang1, Mikkel Algire1, Cheryl H Arrowsmith2, Peter J Brown3, Gary G Chiang1, Jun Guo1, Clarissa G Jakob1, Steven Kennedy3, Fengling Li3, David Maag1, Bailin Shaw1, Nirupama B Soni1, Masoud Vedadi4, William N Pappano1.   

Abstract

A lack of useful small molecule tools has precluded thorough interrogation of the biological function of SMYD2, a lysine methyltransferase with known tumor-suppressor substrates. Systematic exploration of the structure-activity relationships of a previously known benzoxazinone compound led to the synthesis of A-893, a potent and selective SMYD2 inhibitor (IC50: 2.8 nM). A cocrystal structure reveals the origin of enhanced potency, and effective suppression of p53K370 methylation is observed in a lung carcinoma (A549) cell line.

Entities:  

Keywords:  Epigenetics; H3K36; SMYD2; lysine; methyltransferase; p53

Year:  2015        PMID： 26101576      PMCID： PMC4468393          DOI： 10.1021/acsmedchemlett.5b00124

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


  15 in total

1.  Methylation of the retinoblastoma tumor suppressor by SMYD2.

Authors:  Louis A Saddic; Lisandra E West; Aaron Aslanian; John R Yates; Seth M Rubin; Or Gozani; Julien Sage
Journal:  J Biol Chem       Date:  2010-09-24       Impact factor: 5.157

2.  Structural basis of substrate methylation and inhibition of SMYD2.

Authors:  Andrew D Ferguson; Nicholas A Larsen; Tina Howard; Hannah Pollard; Isabelle Green; Christie Grande; Tony Cheung; Renee Garcia-Arenas; Scott Cowen; Jiaquan Wu; Robert Godin; Huawei Chen; Nicholas Keen
Journal:  Structure       Date:  2011-07-21       Impact factor: 5.006

3.  Biochemical characterization of human SET and MYND domain-containing protein 2 methyltransferase.

Authors:  Jiaquan Wu; Tony Cheung; Christie Grande; Andrew D Ferguson; Xiahui Zhu; Kelly Theriault; Erin Code; Cynthia Birr; Nick Keen; Huawei Chen
Journal:  Biochemistry       Date:  2011-06-29       Impact factor: 3.162

4.  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

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

Authors:  Ramzi F Sweis; Marina Pliushchev; Peter J Brown; Jun Guo; Fengling Li; David Maag; Andrew M Petros; Nirupama B Soni; Chris Tse; Masoud Vedadi; Michael R Michaelides; Gary G Chiang; William N Pappano
Journal:  ACS Med Chem Lett       Date:  2014-01-02       Impact factor: 4.345

6.  Overexpression of SMYD2 relates to tumor cell proliferation and malignant outcome of esophageal squamous cell carcinoma.

Authors:  Shuhei Komatsu; Issei Imoto; Hitoshi Tsuda; Ken-ich Kozaki; Tomoki Muramatsu; Yutaka Shimada; Satoshi Aiko; Yutaka Yoshizumi; Daisuke Ichikawa; Eigo Otsuji; Johji Inazawa
Journal:  Carcinogenesis       Date:  2009-05-07       Impact factor: 4.944

7.  The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase.

Authors:  Mohamed Abu-Farha; Jean-Philippe Lambert; Ashraf S Al-Madhoun; Fred Elisma; Ilona S Skerjanc; Daniel Figeys
Journal:  Mol Cell Proteomics       Date:  2007-12-07       Impact factor: 5.911

8.  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

9.  Identification and characterization of Smyd2: a split SET/MYND domain-containing histone H3 lysine 36-specific methyltransferase that interacts with the Sin3 histone deacetylase complex.

Authors:  Mark A Brown; Robert J Sims; Paul D Gottlieb; Philip W Tucker
Journal:  Mol Cancer       Date:  2006-06-28       Impact factor: 27.401

10.  LLY-507, a Cell-active, Potent, and Selective Inhibitor of Protein-lysine Methyltransferase SMYD2.

Authors:  Hannah Nguyen; Abdellah Allali-Hassani; Stephen Antonysamy; Shawn Chang; Lisa Hong Chen; Carmen Curtis; Spencer Emtage; Li Fan; Tarun Gheyi; Fengling Li; Shichong Liu; Joseph R Martin; David Mendel; Jonathan B Olsen; Laura Pelletier; Tatiana Shatseva; Song Wu; Feiyu Fred Zhang; Cheryl H Arrowsmith; Peter J Brown; Robert M Campbell; Benjamin A Garcia; Dalia Barsyte-Lovejoy; Mary Mader; Masoud Vedadi
Journal:  J Biol Chem       Date:  2015-03-30       Impact factor: 5.157
View more
  20 in total

1.  Quantitative Profiling of the Activity of Protein Lysine Methyltransferase SMYD2 Using SILAC-Based Proteomics.

Authors:  Jonathan B Olsen; Xing-Jun Cao; Bomie Han; Lisa Hong Chen; Alexander Horvath; Timothy I Richardson; Robert M Campbell; Benjamin A Garcia; Hannah Nguyen
Journal:  Mol Cell Proteomics       Date:  2016-01-10       Impact factor: 5.911

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.  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

Review 4.  H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development.

Authors:  David S Rogawski; Jolanta Grembecka; Tomasz Cierpicki
Journal:  Future Med Chem       Date:  2016-08-22       Impact factor: 3.808

Review 5.  Histone lysine methyltransferases as anti-cancer targets for drug discovery.

Authors:  Qing Liu; Ming-Wei Wang
Journal:  Acta Pharmacol Sin       Date:  2016-07-11       Impact factor: 6.150

Review 6.  Epigenetic drug discovery: a success story for cofactor interference.

Authors:  A Ganesan
Journal:  Philos Trans R Soc Lond B Biol Sci       Date:  2018-06-05       Impact factor: 6.237

Review 7.  Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease.

Authors:  Kamakoti P Bhat; H Ümit Kaniskan; Jian Jin; Or Gozani
Journal:  Nat Rev Drug Discov       Date:  2021-01-19       Impact factor: 84.694

8.  Structure-Based Design of a Covalent Inhibitor of the SET Domain-Containing Protein 8 (SETD8) Lysine Methyltransferase.

Authors:  Kyle V Butler; Anqi Ma; Wenyu Yu; Fengling Li; Wolfram Tempel; Nicolas Babault; Fabio Pittella-Silva; Jason Shao; Junyi Wang; Minkui Luo; Masoud Vedadi; Peter J Brown; Cheryl H Arrowsmith; Jian Jin
Journal:  J Med Chem       Date:  2016-11-02       Impact factor: 7.446

Review 9.  Lysine methyltransferase inhibitors: where we are now.

Authors:  Alessandra Feoli; Monica Viviano; Alessandra Cipriano; Ciro Milite; Sabrina Castellano; Gianluca Sbardella
Journal:  RSC Chem Biol       Date:  2021-12-13

10.  A chemical probe of CARM1 alters epigenetic plasticity against breast cancer cell invasion.

Authors:  Xiao-Chuan Cai; Tuo Zhang; Eui-Jun Kim; Ming Jiang; Ke Wang; Junyi Wang; Shi Chen; Nawei Zhang; Hong Wu; Fengling Li; Carlo C Dela Seña; Hong Zeng; Victor Vivcharuk; Xiang Niu; Weihong Zheng; Jonghan P Lee; Yuling Chen; Dalia Barsyte; Magda Szewczyk; Taraneh Hajian; Glorymar Ibáñez; Aiping Dong; Ludmila Dombrovski; Zhenyu Zhang; Haiteng Deng; Jinrong Min; Cheryl H Arrowsmith; Linas Mazutis; Lei Shi; Masoud Vedadi; Peter J Brown; Jenny Xiang; Li-Xuan Qin; Wei Xu; Minkui Luo
Journal:  Elife       Date:  2019-10-28       Impact factor: 8.140
View more

北京卡尤迪生物科技股份有限公司 © 2022-2023.