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-λB affinity, K_D of 12 nM) in vitro. DB1976 dihydrochloride 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].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

520.28

C₂₀H₁₈Cl₂N₈Se

2369663-93-2

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

In Vitro: 

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

H₂O : 18.33 mg/mL (35.23 mM; Need ultrasonic)

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.08 mg/mL (4.00 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.08 mg/mL (4.00 mM); Clear solution

  此方案可获得 ≥ 2.08 mg/mL (4.00 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明

• [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.