DDO-2093, a powerful inhibitor of the MLL1-WDR5 protein-protein interaction (IC50 = 8.6 nM; Kd = 11.6 nM), exhibits prominent antitumor effects. Notably, DDO-2093 selectively hampers the catalytic activity of the MLL complex.

DDO-2093 (5 μM; pretreated 7 days) suppresses the expression of MLL-fusion protein dependent genes (HOXA9 and Meis1)[1]. Western Blot Analysis[1] on MV4-11 cells treated at 1, 2.5, 5, and 10 μM for 7 days shows a dose-dependent decrease in the mono-, di-, and trimethylation of H3K4.

DDO-2093, administered intraperitoneally (i.p.) at doses ranging from 20 mg/kg to 80 mg/kg every other day for a duration of 21 days, significantly reduced both the size and weight of tumors in a dose-dependent manner in female nude mice bearing MV4-11 human leukemia cancer xenografts. Specifically, tumor volume growth inhibition (GI) values were observed to increase with higher doses, measuring 13.7% for 20 mg/kg, 37.6% for 40 mg/kg, and 63.9% for 80 mg/kg, respectively.