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CAS No. : 1782235-14-6

MCE 國際站：Laduviglusib trihydrochloride

產(chǎn)品活性：Laduviglusib (CHIR-99021) trihydrochloride 是一種有效的選擇性 GSK-3α/β 抑制劑，IC₅₀ 為 10 nM 和 6.7 nM。CHIR-99021 trihydrochloride 對 GSK-3 的選擇性比 CDC2，ERK2 和其他蛋白激酶高 500 倍以上。Laduviglusib trihydrochloride 還是一種有效的 Wnt/β-catenin 信號通路激活劑。Laduviglusib trihydrochloride 可增強小鼠和人類胚胎干細胞的自我更新。Laduviglusib trihydrochloride 能誘導細胞自噬 (autophagy)。

研究領(lǐng)域：PI3K/Akt/mTOR  |  Stem Cell/Wnt  |  Autophagy

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

In Vitro: Laduviglusib trihydrochloride inhibits human GSK-3β with K_i values of 9.8 nM. Laduviglusib trihydrochloride is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP-binding sites.In vitro kinase assays reveal that Laduviglusib trihydrochloride specifically inhibits GSK3β (IC₅₀=~5 nM) and GSK3α (IC₅₀=~10 nM), with little effect on other kinases. In the presence of Laduviglusib trihydrochloride 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 trihydrochloride 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) trihydrochloride rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3-4 h after administration. Laduviglusib (2 mg/kg) trihydrochloride given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). Laduviglusib trihydrochloride treatment significantly blocks crypt apoptosis and accumulation of p-H2AX⁺ cells, and improves crypt regeneration and villus height. Laduviglusib trihydrochloride 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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