Literature DB >> 28435527

Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment.

Li Li1,2, Xian Jiang2, Shaoqiang Huang2, Zhengxin Ying2, Zhaolan Zhang2, Chenjie Pan2, Sisi Li2, Xiaodong Wang2, Zhiyuan Zhang2,3.   

Abstract

A series of 2-sulfonyl-pyrimidinyl derivatives was developed as apoptosis inhibitors. These represent the first class of apoptosis inhibitors that function through stabilizing mitochondrial respiratory complex II. Starting from a phenotypic screen hit with micromolar activity, we optimized the cellular apoptosis inhibition activity of 2-sulfonyl-pyrimidinyl derivatives to picomolar level (compound 42, also named as TC9-305). The therapeutic potential of these new apoptosis inhibitors was further demonstrated by their neuroprotective effect on an ischemic animal model.

Entities:  

Keywords:  Apoptosis inhibitors; ischemia treatment; mitochondria protection; phenotypic screen; structure−activity optimization

Year:  2017        PMID： 28435527      PMCID： PMC5392758          DOI： 10.1021/acsmedchemlett.6b00489

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


  26 in total

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Authors:  A Gross
Journal:  IUBMB Life       Date:  2001 Sep-Nov       Impact factor: 3.885

Review 2.  Mitochondrial regulation of apoptosis.

Authors:  Bernd Mayer; Rainer Oberbauer
Journal:  News Physiol Sci       Date:  2003-06

3.  Covalent Tethering of Fragments For Covalent Probe Discovery.

Authors:  Stefan G Kathman; Alexander V Statsyuk
Journal:  Medchemcomm       Date:  2016-01-28       Impact factor: 3.597

4.  Structure-activity relationships by interligand NOE-based design and synthesis of antiapoptotic compounds targeting Bid.

Authors:  Barbara Becattini; Carsten Culmsee; Marilisa Leone; Dayong Zhai; Xiyun Zhang; Kevin J Crowell; Michele F Rega; Stefan Landshamer; John C Reed; Nikolaus Plesnila; Maurizio Pellecchia
Journal:  Proc Natl Acad Sci U S A       Date:  2006-08-04       Impact factor: 11.205

Review 5.  Dysregulation of apoptosis as a mechanism of liver disease: an overview.

Authors:  T Patel; L R Roberts; B A Jones; G J Gores
Journal:  Semin Liver Dis       Date:  1998       Impact factor: 6.115

6.  Activation of mitochondrial protease OMA1 by Bax and Bak promotes cytochrome c release during apoptosis.

Authors:  Xian Jiang; Hui Jiang; Zhirong Shen; Xiaodong Wang
Journal:  Proc Natl Acad Sci U S A       Date:  2014-10-01       Impact factor: 11.205

Review 7.  Ischemia-induced neuronal apoptosis.

Authors:  D W Choi
Journal:  Curr Opin Neurobiol       Date:  1996-10       Impact factor: 6.627

Review 8.  "Where, O death, is thy sting?" A brief review of apoptosis biology.

Authors:  Andrew H Wyllie
Journal:  Mol Neurobiol       Date:  2010-06-16       Impact factor: 5.590

9.  A Small Molecule That Protects the Integrity of the Electron Transfer Chain Blocks the Mitochondrial Apoptotic Pathway.

Authors:  Xian Jiang; Li Li; Zhengxin Ying; Chenjie Pan; Shaoqiang Huang; Lin Li; Miaomiao Dai; Bo Yan; Ming Li; Hui Jiang; She Chen; Zhiyuan Zhang; Xiaodong Wang
Journal:  Mol Cell       Date:  2016-07-21       Impact factor: 17.970

Review 10.  Role of apoptosis in disease.

Authors:  Bartolo Favaloro; Nerino Allocati; Vincenzo Graziano; Carmine Di Ilio; Vincenzo De Laurenzi
Journal:  Aging (Albany NY)       Date:  2012-05       Impact factor: 5.682
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  4 in total

Review 1.  Targeting mitochondria for cardiovascular disorders: therapeutic potential and obstacles.

Authors:  Massimo Bonora; Mariusz R Wieckowski; David A Sinclair; Guido Kroemer; Paolo Pinton; Lorenzo Galluzzi
Journal:  Nat Rev Cardiol       Date:  2019-01       Impact factor: 32.419

2.  A small molecule protects mitochondrial integrity by inhibiting mTOR activity.

Authors:  Ran Cao; Li Li; Zhengxin Ying; Zichen Cao; Yongfen Ma; Xiaoxu Mao; Jiaojiao Li; Xiangbing Qi; Zhiyuan Zhang; Xiaodong Wang
Journal:  Proc Natl Acad Sci U S A       Date:  2019-10-25       Impact factor: 11.205

3.  Synthesis, characterization, and antimicrobial evaluation of novel 5-benzoyl-N-substituted amino- and 5-benzoyl-N-sulfonylamino-4-alkylsulfanyl-2-pyridones.

Authors:  Galal Elgemeie; Farag Altalbawy; Mohammed Alfaidi; Rania Azab; Atef Hassan
Journal:  Drug Des Devel Ther       Date:  2017-11-28       Impact factor: 4.162

4.  2-Sulfonylpyrimidines as Privileged Warheads for the Development of S. aureus Sortase A Inhibitors.

Authors:  Fabian Barthels; Jessica Meyr; Stefan J Hammerschmidt; Tessa Marciniak; Hans-Joachim Räder; Wilma Ziebuhr; Bernd Engels; Tanja Schirmeister
Journal:  Front Mol Biosci       Date:  2022-01-03
  4 in total

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