BRD3731

BRD3731 is a highly potent and selective glycogen synthase kinase 3 beta (GSK3β) inhibitor, exhibiting an IC₅₀ value of 15 nM for GSK3β and a 14-fold selectivity over GSK3α (IC₅₀ = 215 nM). It demonstrates excellent kinase selectivity across a broad panel of 311 kinases. Although its inhibitory activity is moderately reduced against the GSK3β D133E mutant (IC₅₀ = 53 nM), BRD3731 retains strong target engagement.

In cellular models, BRD3731 modulates key downstream signaling pathways associated with GSK3β inhibition. In HL-60 acute myeloid leukemia (AML) cells, BRD3731 induces β-catenin stabilization at concentrations starting from 20 μM by reducing phosphorylation at the S33/37/T41 residues and promoting phosphorylation at S675, resulting in elevated total β-catenin levels. Additionally, BRD3731 inhibits CRMP2 phosphorylation in SH-SY5Y neuroblastoma cells, confirming its functional activity in neuronal signaling pathways. Functionally, BRD3731 suppresses colony formation in TF-1 cells while enhancing clonogenic growth in MV4-11 cells, indicating cell-type-dependent biological effects. Collectively, BRD3731 represents a valuable research-grade small-molecule inhibitor for studying GSK3β-mediated signaling in oncology and neurobiology research.