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

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

  • ACS Med Chem Lett. 2017 Mar 1;8(4):407-412. doi: 10.1021/acsmedchemlett.6b00489.
Li Li 1 2,  Xian Jiang 2,  Shaoqiang Huang 2,  Zhengxin Ying 2,  Zhaolan Zhang 2,  Chenjie Pan 2,  Sisi Li 2,  Xiaodong Wang 2,  Zhiyuan Zhang 2 3
Affiliations

Affiliations

  • 1 School of Life Sciences, Peking University, Beijing 100871, China.
  • 2 National Institute of Biological Sciences (NIBS), Beijing 102206, China.
  • 3 Collaborative Innovation Center for Cancer Medicine, Beijing 102206, China.
PMID: 28435527 DOI: 10.1021/acsmedchemlett.6b00489
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.

Keywords

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

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