ASH1L inhibitor AS-85 (AS85) is a first-in-class, potent, selective inhibitor of ASH1L histone methyltransferase with IC50 of 0.6 uM. AS-85 binds to the ASH1L SET domain with Kd value of 0.78 uM. AS-85 inhibits the growth of leukemia cells (MV4;11, MOLM13, and KOPN8) harboring different MLL1 translocations, with GI50 values ranging from 5 µM to 25 µM, and demonstrates no effect in K562 leukemia cells without MLL1 translocations.
