I--BET151

I-BET151 is an isoxazole class pan-BET family inhibitor, blocking BRD2, BRD3, and BRD4 with IC50 values of 0.5, 0.25, and 0.79 µM, respectively. Through this action, it blocks the growth of leukemic cell lines driven by mixed lineage leukemia (MLL) fusions at nanomolar concentrations, whereas tyrosine kinase activated cells were much less sensitive. Specifically, I-BET151 induces apoptosis via reduced expression of BCL2 or triggers G0/G1 cell cycle arrest in MLL-fusion cell lines. I-BET151 is effective in vivo, suppressing MLL leukemia progression in two different mouse models.