APG-1387 是一种二价 SMAC 模拟物，是IAP拮抗剂，可阻断 IAP 家族蛋白 (XIAP，cIAP-1，cIAP-2 和 ML-IAP) 的活性。APG-1387 诱导 cIAP-1 和 XIAP 蛋白降解以及 caspase-3 激活和 PARP 裂解，从而导致细胞凋亡。APG-1387 可用于肝细胞癌，卵巢癌和鼻咽癌的研究。
| 生物活性 | APG-1387, a bivalent SMAC mimetic and anIAPantagonist, blocks the activity of IAPs family proteins (XIAP,cIAP-1,cIAP-2, and ML-IAP). APG-1387 induces degradation ofcIAP-1andXIAPproteins, as well as caspase-3 activation andPARPcleavage, which leads toapoptosis. APG-1387 can be used for the research of hepatocellular carcinoma, ovariancancer, and nasopharyngeal carcinoma[1][2][3][4][5]. |
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体外研究
(In Vitro) | APG-1387 (0.02-20 μM; 24 h) induces rapid degradation of cIAPs in HepG2 and HCCLM3 cells[1].
APG-1387 (2 μM; 24 h) enhances TNF-α- and TRAIL-mediated anti-cancer activities in HepG2 and HCCLM3 cells. APG-1387 sensitizes HepG2 and HCCLM3 cells to NK cell-mediated killing in vitro[1].
Western Blot Analysis[1] | Cell Line: | HepG2 and HCCLM3 cells | | Concentration: | 0.02, 0.2, 2, 20 μM | | Incubation Time: | 1, 6, 24 hours | | Result: | Decreased the expression of cIAP1 and cIAP2 in both cell lines in a dose- and time-dependent manner.
Inhibited the expression of X chromosome-linked IAP (XIAP) at a high dose. |
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体内研究
(In Vivo) | APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) sensitizes HCCLM3 tumors toward NK cell-mediated killing in mice[1].
APG-1387 (20 mg/kg; i.p. every 3 days for 4 weeks) monotherapy exhibits some degree of anti-tumor effect and is well tolerated in mice[1].
| Animal Model: | Non-obese diabetic and severe combined immunodeficiency (NOD-SCID) mice bearing HCCLM3 tumors are injected with NK cells[1] | | Dosage: | 20 mg/kg | | Administration: | I.p. every 3 days for 4 weeks | | Result: | Decreased the expression of cIAP1 and cIAP2, and less potent to XIAP expression.
Potentiated the effects of pre-activated NK cells on HCCLM3 xenograft tumor growth and tumor weight. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(43.20 mM;Need ultrasonic) H2O :< 0.1 mg/mL(insoluble) 配制储备液 | 1 mM | 0.8640 mL | 4.3200 mL | 8.6401 mL | | 5 mM | 0.1728 mL | 0.8640 mL | 1.7280 mL | | 10 mM | 0.0864 mL | 0.4320 mL | 0.8640 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-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: ≥ 2.5 mg/mL (2.16 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (2.16 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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: 2.5 mg/mL (2.16 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (2.16 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 25.0 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: ≥ 2.5 mg/mL (2.16 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (2.16 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 25.0 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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