BH3I-1

300817-68-9

400.31

DMSO : >= 4.1 mg/mL (10.24 mM)

Metabolic Enzyme/Protease; Apoptosis; Apoptosis

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 uM in FP assay. BH3I-1 has a K_d of 5.3 uM against the p53/MDM2 pair. IC50 & Target: Bcl-2^[1]
Kd: 5.3 uM (p53/mDM2)^[2] 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-1alpha 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 uM 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 uM^[3].