Laduviglusib 3HCl is an effective and selective inhibitor of GSK-3α/β, with IC50 values of 10 nM and 6.7 nM, respectively, acting through competitive binding at the ATP site to inhibit GSK3α and GSK3β. It is over 500 times more selective for GSK-3 than for CDC2, ERK2, and other protein kinases. Laduviglusib 3HCl is also an effective activator of the Wnt/β-catenin signaling pathway. It enhances self-renewal in both mouse and human embryonic stem cells and induces autophagy[1][2][3]. At a concentration of 2.5 μM, Laduviglusib 3HCl treatment reduces the viability of ES-D3 cells by 24.7%, at 5 μM by 56.3%, at 7.5 μM by 61.9%, and at 10 μM by 69.2%, with an IC50 of 4.9 μM[2].
Laduviglusib 3HCl 动物研究
Animal study
In ZDF rats, a single oral dose of Laduviglusib 3HCl (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose levels, with the maximum reduction of nearly 150 mg/dl occurring 3-4 hours post-administration[1]. A single dose of Laduviglusib 3HCl (2 mg/kg) administered 4 hours before irradiation significantly improves survival rates following 14.5 Gy abdominal irradiation (ABI). Treatment with Laduviglusib 3HCl significantly blocks crypt apoptosis and the accumulation of p-H2AX+ cells, and improves crypt regeneration and villus height. The treatment increases the survival of Lgr5+ cells by blocking apoptosis and effectively prevents the reduction of Olfm4, Lgr5, and CD44 as early as 4 hours[5].
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