DB1976 (dihydrochloride)

2369663-93-2

520.28

DMSO : 62.5 mg/mL (120.13 mM; Need ultrasonic)

Apoptosis

DB1976 dihydrochloride is a selenophene analog of DB270 and a potent and cell-permeable fully efficacious transcription factor PU.1 inhibitor. DB1976 dihydrochloride potently inhibits PU.1 binding (IC₅₀ of 10 nM) and strongly inhibits the PU.1/DNA complex (with high DB1976-lambdaB affinity, K_D of 12 nM) in vitro. DB1976 dihydrochloride has apoptosis-inducing effect^[1][2][3]. IC50 & Target: IC50: 10 nM (Transcription factor PU.1)^[1] In Vitro: DB1976 is a classic heterocyclic dication (a single heteroatom) with strong affinity and selectivity for AT-rich sequences commonly found in cognate DNA binding sites for PU.1^[2].
DB1976 inhibits PU.1-dependent transactivation of the reporter in a dose-dependent manner with an IC₅₀ value of 2.4 uM in PU.1-negative HEK293 cells^[3].
DB1976 treatment leads to a profound decrease in the growth of PU.1 URE^-/- AML cells (IC₅₀ of 105 uM), while showing little effect on normal hematopoietic cells at similar concentrations (IC₅₀ of 334 uM)^[3].
DB1976 treatment leads to a 1.6-fold increase in apoptotic cells in murine PU.1 URE^-/- AML cells, and observed similar effects in human MOLM13 cells^[3].
DB1976 treatment leads to a significant decrease in the number of viable cells (primary human AML cells) (mean decrease of 81%) and clonogenic capacity (mean decrease of 36%) compared with vehicle-treated cells. The apoptotic cell fraction increased on average by 1.5-fold with DB1976^[3].