BH3I-1 is a Bcl-2 family antagonist, which inhibits the binding of the Bak BH3 peptide to Bcl-xL with a K_i of 2.4±0.2 μM in FP assay. BH3I-1 has a K_d of 5.3 μM against the p53/MDM2 pair.

BH3I-1, while inhibiting its reported target Bcl-2/Bim and Bcl-xL/Bim, shows significant inhibition of both the p53/hDM2 and p300/Hif-1α interactions. This surprising promiscuity, displays by a well studied compound leads to further interrogate the p53/hDM2 interaction utilizing a standard fluorescence polarization (FP) assay with purified protein. The results from the FP assay validates the split-luciferase screen and demonstrates that BH3I-1 has a K_d=5.3 μM against the p53/mDM2 pair, which is comparable to its low micromolar potency reported for the BH3 family of receptors^[2]. BH3I-1 inhibits interaction between the BH3 domain and Bcl-xL. NMR analyses reveal that BH3I-1 targets the BH3-binding pocket of Bcl-xL with a K_i of 7.8±0.9 μM^[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.

400.31

C₁₅H₁₄BrNO₃S₂

300817-68-9

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 4.1 mg/mL (10.24 mM)

* “≥” means soluble, but saturation unknown.

*

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。-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。

• [1]. Wang L, et al. Development of dimeric modulators for anti-apoptotic Bcl-2 proteins. Bioorg Med Chem Lett. 2008 Jan 1;18(1):236-40.

  [2]. Degterev A, et al. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol. 2001 Feb;3(2):173-82.

  [3]. Porter JR, et al. Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2. Chem Commun (Camb). 2010 Nov 14;46(42):8020-2.

Jurkat cells overexpressing Bcl-xL, FL 5.12 and FL 5.12/Bcl-xL cells (5×10⁴ cells per well) are seeded into white 96-well plates and treated with various concentrations of the compounds (e.g., BH3I-1; 30 μM and 90 μM)for 48 h. For zVAD-FMK protection experiments, cells are preincubated with 100 μM zVAD-FMK for 1 h before the addition of chemicals. Cell viability is determined with an MTS assay with a Victor plate reader. For PI staining experiments, cells are grown in 24-well plates and then incubated with 2 μg/mL PI. Cell death is determined by FACS analysis in a FACSCalibur machine^[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.

• [1]. Wang L, et al. Development of dimeric modulators for anti-apoptotic Bcl-2 proteins. Bioorg Med Chem Lett. 2008 Jan 1;18(1):236-40.

  [2]. Degterev A, et al. Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-xL. Nat Cell Biol. 2001 Feb;3(2):173-82.

  [3]. Porter JR, et al. Profiling small molecule inhibitors against helix-receptor interactions: the Bcl-2 family inhibitor BH3I-1 potently inhibits p53/hDM2. Chem Commun (Camb). 2010 Nov 14;46(42):8020-2.