1557397-51-9

1557397-51-9 structure

Name: DB1976
Chemical Name: DB1976
CAS Number: 1557397-51-9
Molecular Formula: C₂₀H₁₆N₈Se
Molecular Weight: 447.35
Catalog: Signaling Pathways Apoptosis Apoptosis
Create Date: 2020-04-08 17:32:29
Modify Date: 2024-01-10 20:34:20
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, KD of 12 nM) in vitro. DB1976 has apoptosis-inducing effect[1][2][3].

Name	DB1976

Description	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, KD of 12 nM) in vitro. DB1976 has apoptosis-inducing effect[1][2][3].
Related Catalog	Signaling Pathways >> Apoptosis >> Apoptosis Research Areas >> Cancer
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 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].
References	[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. [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. [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.

Molecular Formula	C₂₀H₁₆N₈Se
Molecular Weight	447.35

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