ML390

Description: ML390 is a novel potent inhibitor of human DHODH (Dihydroorotate dehydrogenase) that induces differentiation in acute myeloid leukemia (AML) with EC50 of 1.8uM, 8.8uM, 6.5uM, and 0.56uM in ER-HOX-GFP, U937, THP-1 cells and DHODH enzyme, respectively. ML390 was identified as the most potent compound against the engineered ERHOX-GFP cell line. Moreover, the addition of uridine to the cell culture media could abrogate the differentiation effects of ML390, demonstrating further evidences that ML390’ effects were due to their inhibition of DHODH-catalyzed pyrimidine synthesis. Therefore, ML390 may offer insight into the mechanism of overcoming differentiation arrest, and has the potential to used as a treatment for patients with AML.

References: ACS Med Chem Lett. 2016 Sep 28; 7(12):1112-1117; Cell. 2016 Sep 22; 167(1):171-186.e15.