YM-244769 是一种有效的、选择性的、具有口服活性的 Na+/Ca2+交换体 (NCX) 抑制剂。YM-244769 优先抑制NCX3，抑制 NCX 单向向外电流 (Ca2+进入模式)，IC50值分别为 18 nM 和 50 nM。YM-244769 可有效预防缺氧/复氧诱导的 SH-SY5Y 神经元细胞损伤。YM-244769 还能增加小鼠的尿量和尿液中电解质的排泄。
| 生物活性 | YM-244769 is a potent, selective and orally active Na+/Ca2+exchanger (NCX) inhibitor. YM-244769 preferentially inhibitsNCX3and suppresses the unidirectional outward NCX current (Ca2+entry mode), withIC50s of 18 nM and 50 nM, respectively. YM-244769 efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage. YM-244769 can also increase urine volume and urinary excretion of electrolytes in mice[1][2][3]. |
| IC50& Target | IC50: 18 nM (NCX3), 68 nM (NCX1), 96 nM (NCX2)[1] |
体外研究
(In Vitro) | YM-244769 (0.003-1 μM) inhibits dose dependently the initial rates of45Ca2+uptake into NCX1, NCX2, and NCX3 transfectants with IC50values of 68 ± 2.9, 96 ± 3.5, and 18 ± 1.0 nM, respectively[1].
YM-244769 (0.3 or 1 μM) efficiently protects against the hypoxia/reoxygenation-induced lactate dehydrogenase (LDH) release in SH-SY5Y cells and in LLC-PK1cells (1 μM)[1].
YM-244769 possesses reverse mode-selectivity[1].
YM-244769 (1 and 10 μM) inhibits NCX current (INCX) in a concentration- and [Na+]i-dependent manner, the IC50against the unidirectional outward INCX(Ca2+entry mode) is 0.05 μM. The IC50values against the bidirectional outward and inward INCXare similar and approximately 100 nM with a Hill coefficient of about 1[3].
YM-244769 is trypsin-insensitive[3].
Cell Viability Assay[1] | Cell Line: | SH-SY5Y cells treated with NCX1 or NCX3 antisense | | Concentration: | 0.3 and 1 μM | | Incubation Time: | | | Result: | Hypoxia/reoxygenation-induced LDH release was significantly attenuated: reduction in cell damage was greater in cells treated with NCX3 antisense (by 61%) than in cells treated with NCX1 antisense (by 35%).
0.3 or 1 μM efficiently suppressed the hypoxia/reoxygenation-induced cell damage in SH-SY5Y cells treated with NCX1 antisense more than in those treated with NCX3 antisense. |
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体内研究
(In Vivo) | YM-244769 (0.1-1 mg/kg; p.o.; once) exhibits dose-dependently natriuretic action in mice and significantly increases urinary excretion of Ca2+as well as Ca2+/Cr ratio[2].
| Animal Model: | Wild-type C57BL/6J mice and NCX-KO mice[2] | | Dosage: | 0.1, 0.3 and 1 mg/kg | | Administration: | Oral administration, once | | Result: | Caused a dose-dependent increase (up to approximately 200%) in urine volume and urinary excretion of electrolytes (Na+, K+and Cl-). Natriuretic actions were equivalently observed in NCX1-KO and WT, but disappeared in NCX2-KO and double KO. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 120 mg/mL(270.59 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.2549 mL | 11.2747 mL | 22.5494 mL | | 5 mM | 0.4510 mL | 2.2549 mL | 4.5099 mL | | 10 mM | 0.2255 mL | 1.1275 mL | 2.2549 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 (sealed storage, away from moisture)。-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 90%corn oil Solubility: ≥ 2.08 mg/mL (4.69 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (4.69 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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