CHIR-99021 HCl (Laduviglusib HCl) is a highly potent and selective inhibitor of GSK-3α/β, with IC50 values of 10 nM and 6.7 nM respectively. It demonstrates remarkable selectivity for GSK-3, with over 500-fold selectivity over CDC2, ERK2, and other protein kinases. Additionally, CHIR-99021 HCl serves as a robust activator of the Wnt/β-catenin signaling pathway. Moreover, it exhibits the ability to enhance self-renewal in both mouse and human embryonic stem cells. Furthermore, CHIR-99021 HCl induces autophagy [1] [2] [3].

CHIR-99021 hydrochloride抑制人类GSK-3β，其K i 值为9.8 nM [1]。该化合物是一种小分子有机物，通过竞争ATP结合位点抑制GSK3α和GSK3β。体外激酶实验显示，CHIR-99021 hydrochloride特异性抑制GSK3β（IC 50约5 nM）和GSK3α（IC 50约10 nM），对其他激酶的影响较小[4]。在CHIR-99021 hydrochloride作用下，ES-D3细胞的存活率在2.5 μM时降低24.7%，在5 μM时降低56.3%，在7.5 μM时降低61.9%，在10 μM时降低69.2%，其IC 50为4.9 μM [2]。

在ZDF大鼠中，Laduviglusib hydrochloride 口服单次剂量（16 mg/kg 或 48 mg/kg）能迅速降低血浆葡萄糖浓度，最大降幅接近150 mg/dl，发生于给药后3-4小时[1]。Laduviglusib hydrochloride （2 mg/kg）单次给药，于辐射前4小时，能显著提高14.5 Gy腹部辐射（ABI）后的存活率。Laduviglusib hydrochloride 治疗显著阻断隐窝细胞凋亡和p-H2AX + 细胞积累，促进隐窝再生和绒毛高度的增加。Laduviglusib hydrochloride 治疗通过阻断凋亡增加了Lgr5+细胞存活，并有效阻止Olfm4、Lgr5和CD44的减少，作用最快可在4小时内显现[5]。