CHIR-98014

CHIR-98014 is a potent and selective small molecule inhibitor of glycogen synthase kinase 3 (GSK3), targeting both the alpha (GSK3A) and beta (GSK3B) isoforms with high affinity. Originally developed by Chiron Corporation, it acts as an ATP-competitive antagonist. In the context of oncology, CHIR-98014 has been studied for its ability to sensitize MLL-rearranged (MLLr) leukemia cells to BET inhibitors by targeting the SPOP/TRIM24/GSK3 signaling axis, which is implicated in drug resistance. Preclinical data suggests that CHIR-98014 can work synergistically with BET inhibitors to reduce tumor progression in xenograft models. Although it is a significant tool compound in biochemical and cellular research, it has primarily been used in preclinical settings and is widely available as a research reagent.