Laduviglusib (CHIR-99021) 是一种有效的，选择性的，具有口服活性的GSK-3α/β抑制剂，IC50为 10 nM 和 6.7 nM。Laduviglusib 对GSK-3的选择性比 CDC2，ERK2 和其他蛋白激酶高 500 倍以上。Laduviglusib 还是一种有效的Wnt/β-catenin信号通路激活剂。CHIR-99021 可增强小鼠和人类胚胎干细胞的自我更新。Laduviglusib 能诱导细胞自噬 (autophagy)。
| 生物活性 | Laduviglusib (CHIR-99021) is a potent, selective and orally activeGSK-3α/βinhibitor withIC50s of 10 nM and 6.7 nM. Laduviglusib shows >500-fold selectivity forGSK-3over CDC2,ERK2and other protein kinases. Laduviglusib is also a potentWnt/β-cateninsignaling pathway activator. Laduviglusib enhances mouse and human embryonic stem cells self-renewal. Laduviglusib inducesautophagy[1][2][3]. |
| IC50& Target[1] | GSK-3β 6.7 nM (IC50) | GSK-3α 10 nM (IC50) | cdc2 8800 nM (IC50) |
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体外研究
(In Vitro) | Laduviglusib (1-10 μM, 3 days) reduces the viability of the ES-D3 cells with an IC50of 4.9 μM[2].
Laduviglusib (5 μM, 48 h) activates the canonical Wnt-pathway in ES-D3 cells and ES-CCE cells[2].
Laduviglusib (3 μM, 4 days) inhibits ES cell differentiation into neural cells[3].
Laduviglusib (1 μM, 2 weeks) inhibits adipogenesis by blocking induction of C/EBPα and PPARγ in 3T3-L1 preadipocytes[4].
Laduviglusib (2.5 μM, 24 h) protects Lgr5+ cells against radiation-induced apoptosis[5].
Cell Viability Assay[2] | Cell Line: | ES-D3 cells | | Concentration: | 1-10 μM | | Incubation Time: | 3 days | | Result: | Reduced the viability of the ES-D3 cells by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM |
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体内研究
(In Vivo) | Laduviglusib (30 mg/kg, p.o ) rapidly lowers plasma glucose[1].
Laduviglusib (2 mg/kg, i.p.) protects mice against radiation-induced lethal GI injury[5].
| Animal Model: | ZDF rats[1] | | Dosage: | 30 mg/kg | | Administration: | Oral administration | | Result: | Lowered plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration. |
| Animal Model: | WT C57BL/6 mice[5] | | Dosage: | 2 mg/kg | | Administration: | Intraperitoneal injection (i.p.) | | Result: | Blocked crypt apoptosis and increased Lgr5+ cell survival. |
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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 : 16.67 mg/mL(35.82 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.1490 mL | 10.7448 mL | 21.4897 mL | | 5 mM | 0.4298 mL | 2.1490 mL | 4.2979 mL | | 10 mM | 0.2149 mL | 1.0745 mL | 2.1490 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： 0.5%CMC-Na/saline water Solubility: 5 mg/mL (10.74 mM); Suspended solution; Need ultrasonic 2. 请依序添加每种溶剂： 20%SBE-β-CDadjusted to pH 4-4.5 with 1 N acetic Solubility: 5 mg/mL (10.74 mM); Clear solution; Need ultrasonic 3. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.08 mg/mL (4.47 mM); Clear solution
此方案可获得 ≥ 2.08 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 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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