GSK-3β inhibitor 28 is a selective, non-competitive inhibitor of glycogen synthase kinase-3β (GSK-3β), with an IC50 value of 14.82 nM. It enhances the expression of phosphorylated GSK-3β while reducing the levels of p-NF-κB, P65, C-myc, and Cyclin D1. This compound induces apoptosis, causes G1 phase arrest, and inhibits cell migration. GSK-3β inhibitor 28 is applicable for cancer research, including studies on colorectal cancer.

GSK-3β:14.82 nM

GSK-3β inhibitor 28 (Compound 7f) demonstrates potent inhibitory activity against SW480, MDA-MB-231, and A549 cells with IC50 values of 14.58, 14.61, and 19.15 μM, respectively; however, it exhibits weaker activity against MoLM13 (IC50 = 25.75 μM) and HepG2 cells (IC50 = 51.51 μM). At 1 μM, GSK-3β inhibitor 28 shows good selectivity among most kinases (MAPK, EGFR, Src), but only moderate inhibition of GSK-3α, with a 58.0% inhibition rate. The IC50 values for GSK-3β inhibitor 28 range from 0.78 to 25 μM over 72 hours with LX-2 (liver stellate cells) and MIHA (normal liver cells), both being greater than 25 μM. This compound (5-20 μM, 24 h) inhibits SW480 cell migration and reduces colony formation， induces apoptosis, and causes G1 phase arrest in SW480 cells. Additionally, GSK-3β inhibitor 28 (10-20 μM, 72 h) upregulates p-GSK-3β expression while downregulating p-NF-κB, P65, C-myc, Cyclin D1, and XIAP protein expression in SW480 cells.