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Birinapant

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Chemical Structure| 1260251-31-7 同义名 : TL32711
CAS号 : 1260251-31-7
货号 : A189229
分子式 : C42H56F2N8O6
纯度 : 98+%
分子量 : 806.941
MDL号 : MFCD25976869
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(148.71 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • cIAP

    cIAP1, Kd:<1 nM

  • XIAP

    XIAP, Kd:45 nM
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
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 26252969
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.24mL

0.25mL

0.12mL

6.20mL

1.24mL

0.62mL

12.39mL

2.48mL

1.24mL
参考文献

[1]Simone Fulda,Domagoj Vucic. Targeting IAP proteins for therapeutic intervention in cancer. Nat Rev Drug Discov. 2012. 11(2), 109-24.

[2]Bhatt S, Pioso M S, Olesinski E A, et al. Reduced Mitochondrial Apoptotic Priming Drives Resistance to BH3 Mimetics in Acute Myeloid Leukemia[J]. Cancer Cell,.2020.38(6), 872-890.

[3]Yijun Deng,et al. Electrophilic Oxidation and [1,2]-Rearrangement of the Biindole Core of Birinapant. ACS Med Chem Lett. 2016. 7(3), 318-23.

[4]Hongxiang Liu,et al. The SMAC mimetic birinapant attenuates lipopolysaccharide-induced liver injury by inhibiting the tumor necrosis factor receptor-associated factor 3 degradation in Kupffer cells. Immunol Lett. 2017. 185, 79-83.

[5]Danielle F Eytan,et al. Combination effects of SMAC mimetic birinapant with TNFα, TRAIL, and docetaxel in preclinical models of HNSCC. Laryngoscope. 2015. 125(3), E118-24.