AS1949490 是一种口服有效的选择性 SHIP2 磷酸酶抑制剂，抑制小鼠 SHIP2、人 SHIP2、人 SHIP1、人 PTEN、人突触小泡磷酸酶和人肌管蛋白的IC50值分别为 0.34、0.62、13、>50、>50 和 >50 μM。AS1949490 增加 Akt 的磷酸化、葡萄糖的消耗和葡萄糖的摄取。AS1949490 激活细胞内胰岛素信号通路。AS1949490 可用于糖尿病的研究。
| 生物活性 | AS1949490 is a potent, orally active, selectiveSHIP2phosphataseinhibitor withIC50values of 0.34, 0.62, 13, >50, >50, and >50 μM for Mouse SHIP2, Human SHIP2, Human SHIP1, HumanPTEN, Human synaptojanin, and Human myotubularin, respectively. AS1949490 increases the phosphorylation ofAkt, glucose consumption and glucose uptake. AS1949490 activates intracellularinsulinsignalling pathways. AS1949490 can be used for research of diabetes[1][2]. |
| IC50& Target | IC50: 0.34 nM (Mouse SHIP2), 0.62 nM (Human SHIP2), 13 nM (Human SHIP1), >50 nM (Human PTEN), >50 nM (Human synaptojanin), and >50 μM (Human myotubularin)[1]. |
体外研究
(In Vitro) | AS1949490 (0-16 μM; 15 min; L6 myotubes) increases insulin-induced phosphorylation of Akt[1].
AS1949490 (0-10 μM; 48 h) activates glucose metabolism and stimulates glucose uptake activity in L6 myotubes[1].
AS1949490 (0-10 μM; 24 h; L6 myotubes) decreases the level of insulin-induced gluconeogenesis[1].
AS1949490 (10 μM; 48 h) activates glucose metabolism via up-regulation of GLUT1 gene in L6 myotubes[2].
Western Blot Analysis[1] | Cell Line: | L6 myotubes | | Concentration: | 0, 4, 8, and 16 μM; 1 nM (insulin) | | Incubation Time: | 15 minutes | | Result: | Increased insulin-induced phosphorylation of Akt in a dose-dependent manner. |
Western Blot Analysis[2] | Cell Line: | L6 myotubes | | Concentration: | 10 μM | | Incubation Time: | 48 hours | | Result: | Increased GLUT1 but not GLUT4 mRNA expression in L6 myotubes. |
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体内研究
(In Vivo) | AS1949490 (300 mg/kg; p.o.; twice daily, for 7 or 10 d) decreases plasma glucose and activates intracellular insulin signalling in diabetic mice[1].
AS1949490 (300 mg/kg; p.o.; once, for 8 h; male ICR mice) suppresses gluconeogenesis and the expression of related genes[1].
| Animal Model: | Male C57BL/KsJ Jcl-dbm mice and db/+db mice[1] | | Dosage: | 300 mg/kg | | Administration: | Oral administration; twice daily, for 7 or 10 days | | Result: | Decreased plasma glucose (23% reduction, relative to vehicle).
Reduced fasting blood glucose (37% reduction, relative to vehicle) and the area under the blood glucose concentration time curve (AUC).
Increased the phosphorylation of GSK3β in the liver without changing the overall levels of GSK3β protein.
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| Animal Model: | Male ICR mice (6 weeks of age)[1] | | Dosage: | 300 mg/kg | | Administration: | Oral administration; once, for 8 hours | | Result: | Reduced an approximately 50% of both PEPCK and G6Pase mRNA levels. |
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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: DMSO : 50 mg/mL(134.45 mM;Need ultrasonic and warming) 配制储备液 | 1 mM | 2.6890 mL | 13.4452 mL | 26.8904 mL | | 5 mM | 0.5378 mL | 2.6890 mL | 5.3781 mL | | 10 mM | 0.2689 mL | 1.3445 mL | 2.6890 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 (5.59 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (5.59 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。 *以上所有助溶剂都可在本网站选购。
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