DB1976 

DB1976 is a selenophene analog of DB270 and a potent and cell-permeable fully efficacious transcription factor PU.1 inhibitor. DB1976 potently inhibits PU.1 binding (IC₅₀ of 10 nM) and strongly inhibits the PU.1/DNA complex (with high DB1976-λB affinity, K_D of 12 nM) in vitro. DB1976 has apoptosis-inducing effect^[1][2][3].

IC50: 10 nM (Transcription factor PU.1)^[1]

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 μM 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 μM), while showing little effect on normal hematopoietic cells at similar concentrations (IC₅₀ of 334 μM)^[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

447.35

C₂₀H₁₆N₈Se

1557397-51-9

N=C(C1=CC=C2N=C(C3=CC=C(C4=NC5=CC=C(C(N)=N)C=C5N4)[Se]3)NC2=C1)N

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Munde M, et al. Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines. Nucleic Acids Res. 2014 Jan;42(2):1379-90.  [Content Brief]

  [2]. Stephens DC, et al. Pharmacologic efficacy of PU.1 inhibition by heterocyclic dications: a mechanistic analysis. Nucleic Acids Res. 2016 May 19;44(9):4005-13.  [Content Brief]

  [3]. Antony-Debré I, et al. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J Clin Invest. 2017 Dec 1;127(12):4297-4313.  [Content Brief]