tcsc5730 BH3I-1

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.

IC50 & Target: Bcl-2^[1]


Kd: 5.3 μM (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-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].