DDO-2093 dihydrochloride is a potent MLL1-WDR5 protein-protein interaction inhibitor (IC50=8.6 nM; Kd=11.6 nM) with antitumor activity. DDO-2093 dihydrochloride selectively inhibits the catalytic activity of MLL complex[1].
DDO-2093 (5 μM; pretreated 7 days) dihydrochloride 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: | 7 days |
| Result: | Dose-dependently reduced the mono-, di-, and trimethylation of H3K4. |
DDO-2093 (20-80 mg/kg; i.p.; every other day for 21 days) dihydrochloride 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, 40, and 80 mg/kg |
| Administration: | Intraperitoneal injection; every other day for 21 days |
| Result: | Had 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.