BRD0320

BRD0320 is a potent, small-molecule dual inhibitor of glycogen synthase kinase 3 alpha (GSK3α) and glycogen synthase kinase 3 beta (GSK3β). Developed by the Broad Institute, it belongs to the pyrazolo-tetrahydroquinolinone chemical class and acts as an ATP-competitive inhibitor. Unlike paralog-selective inhibitors, BRD0320 concurrently inhibits both GSK3 isoforms, which leads to the stabilization and nuclear translocation of β-catenin, a key component of the WNT signaling pathway. In preclinical research for acute myeloid leukemia (AML), BRD0320 has been utilized to compare the effects of pan-GSK3 inhibition against selective paralog targeting. While it shows activity in reducing disease burden in some AML models, the induction of β-catenin signaling is a significant biological differentiator from selective GSK3α inhibitors like BRD0705.