Birinapant (TL32711) 是一种二价 Smac 模拟物，是XIAP和cIAP1的强效拮抗剂，Kd值分别为 45 nM 和小于 1 nM。Birinapant (TL32711) 诱导完整细胞中 cIAP1 和 cIAP2 的自身泛素化和蛋白酶体降解，从而形成 RIPK1: caspase-8 复合物，caspase-8 活化和诱导肿瘤细胞死亡。Birinapant (TL32711) 靶向与 TRAF2 相关的 cIAP，并消除 TNF 诱导的 NF-κB 活化。
| 生物活性 | Birinapant (TL32711), a bivalent Smac mimetic, is a potent antagonist forXIAPandcIAP1withKds of 45 nM and less than 1 nM, respectively. Birinapant (TL32711) induces the autoubiquitylation and proteasomal degradation ofcIAP1and cIAP2 in intact cells, which results in formation of a RIPK1:caspase-8complex,caspase-8activation, and induction of tumor cell death. Birinapant (TL32711) targets TRAF2-associated cIAPs and abrogates TNF-inducedNF-κBactivation. |
| IC50& Target | Kd: 45 nM (XIAP),<1 nm (ciap1)[1] |
体外研究
(In Vitro) | Birinapant (TL32711) (30-10000 nM; 24 hours) significantly decreases the viability of SUM190 cells in a dose-dependent manner[1].
Birinapant (TL32711) (30-1000 nM; 4 hours) shows a significant decrease in cIAP1 levels and enhanced PARP cleavage, and induces apoptosis[1].
Birinapant (TL32711) binds with high affinity to the isolated BIR3 domains of cIAP1, cIAP2, and XIAP and the single BIR domain of ML-IAP and rapidly degrades TRAF2-bound cIAP1 and cIAP2 thereby inhibiting TNF-mediated NF-κB activation[1].
Cell Viability Assay[1] | Cell Line: | TRAIL-resistant SUM190 IBC cells | | Concentration: | 30, 100, 300, 1000, 10000 nM | | Incubation Time: | 24 hours | | Result: | Significantly decreased the viability of SUM190 cells in a dose-dependent manner. |
Western Blot Analysis[1] | Cell Line: | SUM190 cells | | Concentration: | 30, 300, 1000 nM | | Incubation Time: | 4 hours | | Result: | Showed a significant decrease in cIAP1 levels and enhanced PARP cleavage. |
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体内研究
(In Vivo) | Birinapant (TL32711) (30 mg/kg; i.p.; every third day (*5)) shows antitumor efficacy and are devoid of overt toxicity in preclinical models[2].
| Animal Model: | Female athymic nude mice (low-passage, patient-derived xenotransplant models of ovarian cancer, colorectal cancer, and melanoma)[2] | | Dosage: | 30 mg/kg | | Administration: | Intraperitoneal injection; every third day (*5) | | Result: | Resulted in inhibition of tumor growth. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 125 mg/mL(154.91 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.2392 mL | 6.1962 mL | 12.3925 mL | | 5 mM | 0.2478 mL | 1.2392 mL | 2.4785 mL | | 10 mM | 0.1239 mL | 0.6196 mL | 1.2392 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (2.58 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (2.58 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 2.08 mg/mL (2.58 mM); Suspended solution; Need ultrasonic
此方案可获得 2.08 mg/mL (2.58 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 3. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (2.58 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (2.58 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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