Inhibitor of apoptosis (IAP) proteins exert a range of biological activities that promote cancer cell survival and proliferation. X chromosome-linked IAP is a direct inhibitor of caspases, pro-apoptotic executioner proteases, whereas cellular IAP proteins block the assembly of pro-apoptotic protein signalling complexes and mediate the expression of anti-apoptotic molecules[3].
Birinapant is a synthetic small molecule that is both a peptidomimetic of second mitochondrial-derived activator of caspases (SMAC) and inhibitor of IAP family proteins, with potential antineoplastic activity. Birinapant binds with XIAP and cIAP1 with K of 45 and <1 nM, respectively.[4]. Birinapant-mediated activation of cIAP1 resulted in cIAP1 autoubiquitylation and degradation and correlated with inhibition of TNF-mediated NF-κB activation, induction of tumor cell death in vitro, and tumor regression in vivo[5]. Birinapant significantly improved the survival rate of endotoxemic mice (P<0.05) and attenuated LPS-induced liver pathologic damage and inflammatory response. IL-1 and TNF-α levels, and cIAP1 expression in liver resident macrophage (Kupffer cells, KCs) was significantly decreased in the Birinapant group compare with the controlled group[6]. Birinapant, alone or in combination with TNFα or TRAIL, decreased cell density in cell lines, with IC50 s ranging from 0.5 nM to > 1 µM. Birinapant alone or with TNF significantly increased subG0 cell death in different lines[7].
Birinapant 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
451Lu
Growth Inhibition Assay
72 h
IC50=14.2 nM, combined with 1ng/ml TNF-α
23403634
Molm13
2/20/200 nM
Function Assay
24 h
decreases cIAP1 and, to a much lesser extent, cIAP2, and XIAP under various conditions
24526787
PANC-1
50/200/500 nM
Growth Inhibition Assay
0-96 h
inhibits cell growth in both time and dose dependent manner
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