Cilengitide (EMD 121974) 是一种强效的整合素拮抗剂，IC50分别为 0.61 nM (ανβ3)，8.4 nM (ανβ5) 和 14.9 nM (α5β1)。Cilengitide 抑制ανβ3和ανβ5与玻连蛋白结合，IC50值分别为 4 和 79 nM。Cilengitide 能够抑制TGF-β/Smad信号通路，调节PD-L1表达。Cilengitide 诱导凋亡 (apoptosis)，在对胶质母细胞瘤和其他癌症的研究中也显示出抗血管生成的作用。
| 生物活性 | Cilengitide (EMD 121974) is a potentintegrinsantagonist withIC50s of 0.61 nM (ανβ3), 8.4 nM (ανβ5) and 14.9 nM (α5β1), respectively. Cilengitide inhibits the binding ofανβ3andανβ5to Vitronectin withIC50s of 4 nM and 79 nM, respectively. Cilengitide inhibitsTGF-β/Smadsignaling, mediatesPD-L1expression. Cilengitide also inducesapoptosis, shows antiangiogenic effect in the research against glioblastoma and other cancers[1][2][3]. |
| IC50& Target[1][2][3] | αvβ3 4 nM (IC50, αvβ3-Vitronectin interaction[2]) | αvβ5 79 nM (IC50, αvβ5-Vitronectin interaction[2]) | αvβ3 0.61 nM (IC50,[1]) | αvβ5 8.4 nM (IC50,[1]) | α5β1 14.9 nM (IC50,[1]) | STAT3 |
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体外研究
(In Vitro) | Cilengitide is a cyclized RGD (Arg-Gly-Asp motif)-containing pentapeptide. Cilengitide blocks integrin ανβ3- and ανβ5-mediated endothelial cell attachment and migration[2].
Cilengitide inhibits integrin-mediated binding to Vitronectin with IC50s of 0.4 and 0.4 μM in cell adhesion studies assessing the human melanoma M21 or UCLA-P3 human lung carcinoma cell lines[2].
Cilengitide inhibits the attachment of human umbilical vein endothelial cells to Vitronectin with an IC50of 2 μM[2].
Cilengitide (0-1 mg/mL; 24-72 h) inhibits cell viability of melanoma cells in vitro and (5 μg/mL; 12 h) induces B16 and A375 cells apoptosis[3].
Cilengitide (5 μg/mL, 10 μg/mL; 2 weeks) inhibits colony formation of B16 and A375 cells[3].
Cilengitide (0-20 μg/mL; 12 h) inhibits STAT3 phosphorylation to decrease the expression of PD-L1[3].
Western Blot Analysis[3] | Cell Line: | B16 and A375 cells | | Concentration: | 0, 5, 10, and 20 μg/mL | | Incubation Time: | 12 hours | | Result: | Suppressed PD-L1 expression and STAT3 phosphorylation at concentrations greater than 5 μg/mL. |
Apoptosis Analysis[3] | Cell Line: | B16 and A375 cells | | Concentration: | 5 μg/mL | | Incubation Time: | 12 hours | | Result: | Resulted apoptosis rates in B16 and A375 cells of 15.27% and 14.89%, respectively. |
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体内研究
(In Vivo) | Cilengitide (i.p. at 10, 50, and 250 μg three times per week) inhibits M21-L melanoma tumors growth in nude mice[2].
Cilengitide (50 mg/kg; i.p.; daily) enhances the function of CD8+ T cells and promotes anti-PD1 efficacy with Anti-PD1 monoclonal antibody in B16 murine melanoma model[3].
| Animal Model: | Nude mice bearing M21-L melanoma tumors[2] | | Dosage: | 10, 50, and 250 μg | | Administration: | Dosed i.p. three times per week | | Result: | Demonstrated inhibition of tumor growth with a reduction in both tumor volume (55%, 75%, and 89%, respectively) and tumor weight (23%, 38%, and 61%, respectively), when compared to controls. |
| Animal Model: | Female C57BL/6 mice (6-8 weeks old) with B16 cells s.c.[3] | | Dosage: | 50 mg/kg; with or without 10 mg/kg Anti-PD1 monoclonal antibody or isotype control i.p. every 3 days; | | Administration: | Intraperitoneal injection; daily | | Result: | Downregulated the expression of PD-L1 via STAT3 pathway and decreased the expression of PD-L1. |
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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 | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: H2O : 100 mg/mL(169.88 mM;Need ultrasonic) DMSO : ≥ 44 mg/mL(74.75 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.6988 mL | 8.4939 mL | 16.9877 mL | | 5 mM | 0.3398 mL | 1.6988 mL | 3.3975 mL | | 10 mM | 0.1699 mL | 0.8494 mL | 1.6988 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。-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： PBS Solubility: 100 mg/mL (169.88 mM); Clear solution; Need ultrasonic
*以上所有助溶剂都可在本网站选购。 |
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