M-808 is a potent and efficacious covalent inhibitor, targeting the interaction between Menin and MLL. It demonstrates a high binding affinity with an IC50 value of 2.6 nM.

MV-4-11 cells:1 nM (IC50), Menin-MLL (MV4):1 nM (IC50), Menin-MLL (MOLM-13 cells):4 nM (IC50)

M808 demonstrates potent inhibitory activity, with IC50 values of 1 nM, 4 nM, and 2.8 nM against MV4;11, MOLM-13, and HL60 cells, respectively[1]. Additionally, it forms a covalent bond through its acrylamide group with the sulfur atom of Cys329 in menin[1].

M-808 (16) exhibits good tolerability in severe combined immunodeficiency (SCID) mice when administered intravenously at doses of 10 mg/kg or 25 mg/kg on an every-other-day basis (three times a week) over a week. At the 25 mg/kg dosage, M-808 achieves up to 97% maximum tumor growth inhibition (TGI) by treatment day 35, reducing the average tumor volume from 92 mm^3 at the start to 59 mm^3 on day 35, without significant toxicity[1].