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Laduviglusib

CAS No. : 252917-06-9

MCE 站：Laduviglusib

产品活性：Laduviglusib (CHIR-99021) 是一种有效的选择性 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)。

研究领域：PI3K/Akt/mTOR  |  Stem Cell/Wnt  |  Autophagy

作用靶点：GSK-3  |  Wnt  |  β-catenin  |  Autophagy

In Vitro: Laduviglusib (CHIR-99021) inhibits human GSK-3β with K_i values of 9.8 nM. Laduviglusib is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that Laduviglusib specifically inhibits GSK3β (IC₅₀=~5 nM) and GSK3α (IC₅₀=~10 nM), with little effect on other kinases. In the presence of Laduviglusib the viability of the ES-D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM Laduviglusib with an IC₅₀ of 4.9 μM.

In Vivo: In ZDF rats, a single oral dose of Laduviglusib (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration. Laduviglusib (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). Laduviglusib treatment significantly blocks crypt apoptosis and accumulation of p-H2AX⁺ cells, and improves crypt regeneration and villus height. Laduviglusib treatment increases Lgr5⁺ cell survival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h.

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