DB2313

DB2313 is a potent inhibitor of transcription factor PU.1. DB2313 inhibits PU.1-dependent reporter gene transactivation with an IC₅₀ of 5 μM. DB2313 disrupts the interaction of PU.1 with target gene promoters. DB2313 induces apoptosis in acute myeloid leukemia (AML) cells and has anticancer effects^[1]. IC50 & Target:IC50: 14 nM (PU.1)^[1] In Vitro:DB2313 treatment leads to a profound decrease in the growth of PU.1 URE^–/– acute myeloid leukemia (AML) cells (IC₅₀ of 7.1 μM), while showing little effect on normal hematopoietic cells at similar concentrations. DB2313 treatment leads to a 3.5-fold increase in apoptotic cells in murine PU.1 URE^–/– AML cells. DB2313 also leads to a significant decrease in clonogenicity in the second and third rounds of plating and a complete disruption of clonogenic capacity in the fourth and higher rounds of plating^[1].
In AML cells, DB2313 decreases PU.1 occupancy on E2f1, Junb, and Csf1r promoters^[1]. In Vivo:DB2313 (17 mg/kg; i.p.; three times per week; for 3 weeks) treatment decreases leukemia progression and results in increased survival in mice^[1].