生物活性

• 靶点

  cIAP1 Kd:1nM

  XIAP Kd:45nM

• 描述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].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  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	26252969

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• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT01486784	Acute Myelogenous Leukemia	Phase 1 Phase 2	Active, not recruiting	-	United States, Pennsylvania ... more >> Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania, United States, 19104 Collapse <<
  NCT01573780	Unspecified Adult Solid Tumor,... more >> Protocol Specific Collapse <<	Phase 1	Terminated(Sponsor did not hav... more >>e funds to continue study) Collapse <<	-	United States, New York ... more >> Roswell Park Cancer Institute Buffalo, New York, United States, 14263 United States, Pennsylvania Thomas Jefferson University Philadelphia, Pennsylvania, United States, 19107 Collapse <<
  NCT01766622	Ovarian Neoplasms ... more >> Ovarian Cancer Fallopian Tube Neoplasms Fallopian Tube Cancer Collapse <<	Phase 2	Withdrawn	-	-

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