| CAS |
No.300817-68-9 |
| 英文名称 |
BH3I-1 |
| 别名 |
BHI1 |
| 分子式 |
C15H14BrNS2O3 |
| 分子量 |
400.31 |
| 溶解性 |
Soluble in DMSO |
| 纯度 |
≥97% |
| 外观(性状) |
Light yellow to yellow Solid |
| 储存条件 |
Powder:2-8℃，2 years;Insolvent(母液):-20℃，6 months;-80℃，1 year |
| MDL |
MFCD03453544 |
| SMILES |
O=C(O)C(C(C)C)N(C/1=O)C(SC1=C\C2=CC=C(Br)C=C2)=S |
| 靶点 |
Bcl-2 Family;MDM-2/p53 |
| 通路 |
Apoptosis |
| 背景说明 |
BH3I-1是Bcl-XL-BH3 domain interaction抑制剂。它是一种Bcl-2家族蛋白的选择性抑制剂。 |
| 生物活性 |
BH3I-1 is a Bcl-2 family antagonist, which inhibits the binding of the Bak BH3 peptide to Bcl-xL with a Ki of 2.4±0.2 μM in FP assay. BH3I-1 has a Kd of 5.3 μM against the p53/MDM2 pair.[1-3] |
| In Vitro |
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 Kd=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 Ki of 7.8±0.9 μM[3]. |
| 细胞实验 |
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]. |
| 数据来源文献 |
[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. |
| 规格 |
5mg 10mg 25mg 50mg 100mg |
| 单位 |
瓶 |
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