Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic
Design, synthesis, and evaluation of a potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase (Smac) mimetic
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DOI：
10.1021/jm061108d
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发表时间：
2006-12-28
影响因子：
7.3
通讯作者：
Wang, Shaomeng
中科院分区：
文献类型：
--
作者：
Sun, Haiying;Nikolovska-Coleska, Zaneta;Wang, Shaomeng
设计、合成和评价了一种有效的、细胞渗透性的、构象受限的caspase模拟物线粒体衍生第二激活剂(SM-131，2)。化合物2在竞争结合实验中与X-连锁的凋亡蛋白抑制物(XIAP)结合，K-I为61 nM，并在无细胞功能实验中直接拮抗XIAP对caspase-9活性的抑制。化合物2抑制细胞生长的IC50值为100 nM，并能有效诱导人乳腺癌细胞株MDA-MB-231细胞死亡。
A potent, cell-permeable, conformationally constrained second mitochondria derived activator of caspase mimetic (SM-131, 2) has been designed, synthesized, and evaluated. Compound 2 binds to X-linked inhibitors of apoptosis proteins (XIAP) with a K-i of 61 nM in a competitive binding assay and directly antagonizes the XIAP inhibition of caspase-9 activity in a cell-free functional assay. Compound 2 achieves an IC50 of 100 nM in inhibition of cell growth and effectively induces cell death in the MDA-MB-231 human breast cancer cell line.