A-192621 是一种有效的非肽，口服活性，选择性内皮素 B (ETB) 受体拮抗剂，IC50为 4.5 nM，Ki为 8.8 nM。A-192621 的选择性比 ETA高 636 倍 (IC50为 4280 nM，Ki为 5600 nM)。A-192621 促进 PASMC 细胞凋亡，并引起动脉血压升高和血浆 ET-1 水平升高。
| 生物活性 | A-192621 is a potent, nonpeptide, orally active and selectiveendothelin B (ETB) receptorantagonist with anIC50of 4.5 nM and aKiof 8.8 nM. The selectivity of A-192621 is 636-fold higher thanETA(IC50of 4280 nM andKiof 5600 nM). A-192621 promotesapoptosisin PASMCs. A-192621 alos causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level[1][2][3]. |
| IC50& Target[1] | ETB 4.5 nM (IC50) | ETB 8.8 nM (Ki) | ETA 4280 nM (IC50) | ETA 5600 nM (Ki) |
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体外研究
(In Vitro) | A-192621 (1-100 μM; 48 hours; PASMCs) treatment markedly reduces the cell viability of PASMCs in a dose-dependent manner[2].
A-192621 (1-100 μM; 48 hours; PASMCs) treatment significantly increases the caspase-3/7 activity and cleaved caspase-3 expression in PASMCs. A-192621 induces apoptosis in a dose-dependent manner and increases the cells' susceptibility to apoptosis by Doxorubicin treatment[2].
Cell Viability Assay[2] | Cell Line: | Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin | | Concentration: | 1 μM, 10 μM, 50 μM, 100 μM | | Incubation Time: | 72 hours | | Result: | The viability of PASMCs was significantly decreased in a dose-dependent manner. |
Western Blot Analysis[2] | Cell Line: | Pulmonary arterial smooth muscle cells (PASMCs) with Doxorubicin | | Concentration: | 1 μM, 10 μM, 100 μM | | Incubation Time: | 72 hours | | Result: | The caspase-3/7 activity in PASMCs was significantly increased in a dose-dependent manner. |
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体内研究
(In Vivo) | A-192621 (30-100 mg/kg; oral administration; daily; for 3 days; male Sprague-Dawley rats) treatment inhibits both dilatory and pressor responses induced by S6c mediated by ETBwith an ED50value of 30 mg/kg, and failed to inhibit the ET-1-induced pressor response mediated by ETA. A-192621 alone causes elevation of arterial blood pressure and an elevation in the plasma ET-1 level in the conscious normotensive rat[3].
| Animal Model: | Male Sprague-Dawley rats (250-350 g)[3] | | Dosage: | 30 mg/kg 100 mg/kg | | Administration: | Oral administration; daily; for 3 days | | Result: | Inhibited both dilatory and pressor responses induced by S6c mediated by ETBwith an ED50value of 30 mg/kg. |
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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 : ≥ 100 mg/mL(179.00 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.7900 mL | 8.9500 mL | 17.9000 mL | | 5 mM | 0.3580 mL | 1.7900 mL | 3.5800 mL | | 10 mM | 0.1790 mL | 0.8950 mL | 1.7900 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: ≥ 2.5 mg/mL (4.47 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (4.47 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。 *以上所有助溶剂都可在本网站选购。
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