DDO-2093

DDO-2093 is a potent MLL1-WDR5 protein-protein interaction inhibitor (IC50=8.6 nM; Kd=11.6 nM) with antitumor activity. DDO-2093 selectively inhibits the catalytic activity of MLL complex[1].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

MV4-11(harboring MLL-AF4 fusion protein) and MOLM-13 (harboring MLL-AF9 fusion protein)[1]. DDO-2093 (5 μM; pretreated 7 days) inhibits MLL-fusion protein dependent genes expression (HOXA9 and Meis1)[1]. Western Blot Analysis[1] Cell Line: MV4-11 cells Concentration: 1, 2.5, 5, and 10 μM Incubation Time: Pretreated 7 days Result: Dose-dependently reduced the mono-, di-, and trimethylation of H3K4.

DDO-2093 (20 mg/kg-80 mg/kg; i.p.; every other day for 21 days) significantly suppresses the tumor size and weight in a dose-dependent manner[1]. Animal Model: Female nude mice (MV4-11 human leukemia cancer xenografts)[1] Dosage: 20 mg/kg, 40 mg/kg and 80 mg/kg Administration: I.p.; every other day for 21 days Result: The tumor volume growth inhibition (GI) values were calculated to be 13.7%, 37.6% and 63.9% with doses of 20 mg/kg, 40 mg/kg and 80 mg/kg, respectively.

[1]. Chen W, et al. Discovery of a potent MLL1 and WDR5 protein-protein interaction inhibitor with in vivo antitumor activity [published online ahead of print, 2021 Jun 28]. Eur J Med Chem. 2021;223:113677.