Literature DB >> 25467161

Identification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase.

Benjamin P Fauber1, Peter S Dragovich1, Jinhua Chen2, Laura B Corson1, Charles Z Ding2, Charles Eigenbrot1, Sharada Labadie1, Shiva Malek1, David Peterson1, Hans E Purkey1, Kirk Robarge1, Steve Sideris1, Mark Ultsch1, BinQing Wei1, Ivana Yen1, Qin Yue1, Aihe Zhou1.   

Abstract

A series of 3,6-disubstituted dihydropyrones were identified as inhibitors of human lactate dehydrogenase (LDH)-A. Structure activity relationships were explored and a series of 6,6-spiro analogs led to improvements in LDHA potency (IC50 <350 nM). An X-ray crystal structure of an improved compound bound to human LDHA was obtained and it illustrated additional opportunities to enhance the potency of these compounds, resulting in the identification of 51 (IC50=30 nM).
Copyright © 2014 Elsevier Ltd. All rights reserved.

Entities:  

Keywords:  LDHA; Tumor metabolism; X-ray crystal structure

Mesh：

Substances：

Year:  2014        PMID： 25467161     DOI： 10.1016/j.bmcl.2014.10.067

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  4 in total

1.  Metabolic plasticity underpins innate and acquired resistance to LDHA inhibition.

Authors:  Aaron Boudreau; Hans E Purkey; Anna Hitz; Kirk Robarge; David Peterson; Sharada Labadie; Mandy Kwong; Rebecca Hong; Min Gao; Christopher Del Nagro; Raju Pusapati; Shuguang Ma; Laurent Salphati; Jodie Pang; Aihe Zhou; Tommy Lai; Yingjie Li; Zhongguo Chen; Binqing Wei; Ivana Yen; Steve Sideris; Mark McCleland; Ron Firestein; Laura Corson; Alex Vanderbilt; Simon Williams; Anneleen Daemen; Marcia Belvin; Charles Eigenbrot; Peter K Jackson; Shiva Malek; Georgia Hatzivassiliou; Deepak Sampath; Marie Evangelista; Thomas O'Brien
Journal:  Nat Chem Biol       Date:  2016-08-01       Impact factor: 15.040

2.  Cell Active Hydroxylactam Inhibitors of Human Lactate Dehydrogenase with Oral Bioavailability in Mice.

Authors:  Hans E Purkey; Kirk Robarge; Jinhua Chen; Zhongguo Chen; Laura B Corson; Charles Z Ding; Antonio G DiPasquale; Peter S Dragovich; Charles Eigenbrot; Marie Evangelista; Benjamin P Fauber; Zhenting Gao; Hongxiu Ge; Anna Hitz; Qunh Ho; Sharada S Labadie; Kwong Wah Lai; Wenfeng Liu; Yajing Liu; Chiho Li; Shuguang Ma; Shiva Malek; Thomas O'Brien; Jodie Pang; David Peterson; Laurent Salphati; Steve Sideris; Mark Ultsch; BinQing Wei; Ivana Yen; Qin Yue; Huihui Zhang; Aihe Zhou
Journal:  ACS Med Chem Lett       Date:  2016-08-26       Impact factor: 4.345

Review 3.  Three-Dimensional Analysis of the Interactions between hLDH5 and Its Inhibitors.

Authors:  Giulio Poli; Carlotta Granchi; Mohamed Aissaoui; Filippo Minutolo; Tiziano Tuccinardi
Journal:  Molecules       Date:  2017-12-13       Impact factor: 4.411

4.  LDHA Suppression Altering Metabolism Inhibits Tumor Progress by an Organic Arsenical.

Authors:  Yu-Jiao Liu; Xiao-Yang Fan; An-Dong Wang; Yin-Zheng Xia; Wen-Rong Fu; Jun-Yi Liu; Feng-Lei Jiang; Yi Liu
Journal:  Int J Mol Sci       Date:  2019-12-11       Impact factor: 5.923
  4 in total

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