Biological Activity
epz004777 is a potent and selective inhibitor of dot1l, a protein methyltransferase catalyzing the methylation of lysine 4 of histone h3 (h3k4), with the half maximal inhibition concentration ic50 value of 400 pm [1].epz004777 has been found to concentration-dependently inhibit the h3k79 methylation in a variety of mixed lineage leukemia (mll) cells, including mll-rearranged acute myeloid leukemia (molm-13 and mll-af9), mll-rearranged biphenotypic leukemia (mv4-11 and mll-af4) and non-mll-rearranged t cell acute leukemia cells [1].additionally, epz004777 exhibits anti-proliferative activity against both mll-rearranged and non-rearranged human leukemia cell lines, including rs4;11 (ic50: 6.47 μm), sem (ic50: 1.72 μm), mv4-11 (ic50: 0.17 μm), thp-1 (ic50: 3.36 μm), molm-13 (ic50: 0.72 μm), kopn-8 (ic50: 0.62 μm), reh (ic50: 13.9 μm), kasumi-1 (ic50: 32.99 μm) and 697 (ic50: 36.57 μm) [1].
References
[1] daigle sr, olhava ej, therkelsen ca, majer cr, sneeringer cj, song j, johnston ld, scott mp, smith jj, xiao y, jin l, kuntz kw, chesworth r, moyer mp, bernt km, tseng jc, kung al, armstrong sa, copeland ra, richon vm, pollock rm. selective killing of mixed lineage leukemia cells by a potent small-molecule dot1l inhibitor. cancer cell. 2011 jul 12;20(1):53-65. doi: 10.1016/j.ccr.2011.06.009.
