| Title | Discovery of Highly Potent 2-Sulfonyl-Pyrimidinyl Derivatives for Apoptosis Inhibition and Ischemia Treatment |
| Authors | Li, Li Jiang, Xian Huang, Shaoqiang Ying, Zhengxin Zhang, Zhaolan Pan, Chenjie Li, Sisi Wang, Xiaodong Zhang, Zhiyuan |
| Affiliation | Peking Univ, Sch Life Sci, Beijing 100871, Peoples R China. NIBS, Beijing 102206, Peoples R China. Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China. NIBS, Beijing 102206, Peoples R China. Zhang, ZY (reprint author), Collaborat Innovat Ctr Canc Med, Beijing 102206, Peoples R China. |
| Keywords | Apoptosis inhibitors phenotypic screen structure-activity optimization ischemia treatment mitochondria protection CYTOCHROME-C RELEASE CELL-DEATH BAX DESIGN |
| Issue Date | 2017 |
| Publisher | ACS MEDICINAL CHEMISTRY LETTERS |
| Citation | ACS MEDICINAL CHEMISTRY LETTERS.2017,8(4),407-412. |
| 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. |
| URI | http://hdl.handle.net/20.500.11897/474250 |
| ISSN | 1948-5875 |
| DOI | 10.1021/acsmedchemlett.6b00489 |
| Indexed | SCI(E) |
| Appears in Collections: | 生命科学学院 |
