Laduviglusib（CHIR-99021）,252917-06-9,IC-0121293

CHIR-99021 is the most commonly used GSK-3β inhibitor and is considered the standard small-molecule Wnt agonist.CHIR-99021 is a potent inhibitor with high selectivity[[1].

CHIR-99021 led to a marked recovery in cell growth and viability suppressed by CDX2 overexpression. CHIR-99021 restored the protein levels of cyclin D1, c-myc, and β-catenin inhibited by overexpression of CDX2, as well as the cell growth and viability[2].

When the Human Tenon's fibroblasts(HTFs) were treated with TGF-β, a significant increase in the active form of GSK-3β was observed. A significant decrease in the active form of GSK-3β and molecules associated with fibrosis by TGF-β was noted in HTFs treated with CHIR-99021. CHIR-99021 treatment reduced the phosphorylated Smad2/Smad2 and phosphorylated Smad3/Smad3 ratios in HTFs and attenuated HTF migration[3].

The GSK-3 inhibitor CHIR 99021 trihydrochloride (0–10 mg/kg, ip) was injected 45-min prior to self-administration sessions in a counterbalanced design. After completion of the self-administration dose-effect curve, potential locomotor effects of the GSK-3 inhibitor were assessed. CHIR 99021 (10 mg/kg) dose-dependently increased alcohol reinforced responding with no effect on sucrose self-administration or locomotor activity. CHIR 99021 (10 mg/kg) significantly decreased pGSK-3β expression in all brain regions tested, reduced PICK1 and increased GluA2 total expression only in the NAcb.?Signaling through the GSK-3 / PICK1 / GluA2 molecular pathway drives the positive reinforcing effects of the drug, which are required for abuse liability[4].