BHPI

Description: BHPI is a potent ERalpha inhibitor that blocks nuclear estrogen-ERalpha-regulated gene expression effectively. It triggers sustained ERalpha-dependent activation of the endoplasmic reticulum (EnR) stress sensor, notably the unfolded protein response (UPR), and consistently inhibits protein synthesis. With an IC50 value targeting ERalpha, BHPI's mechanism involves the rapid hyperactivation of PLCgamma on the plasma membrane in ERalpha(+) cancer cells, which produces inositol 1,4,5-triphosphate (IP3). This, in turn, opens EnR IP3R calcium channels, leading to a rapid depletion of EnR Ca(2+) stores. SIGNIFICAN TLY, BHPI alters estrogen-ERalpha's usual effect of causing mild and transient UPR activation by inducing a severe and prolonged UPR activation, transforming the UPR from a protective to a toxic response. Target: Others. Smiles: Cc1cccc2c1NC(=O)C2(c1ccc(O)cc1)c1ccc(O)cc1. References: Andruska ND, et al. Estrogen receptor alpha inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression. Proc Natl Acad Sci U S A. 2015 Apr 14,112(15):4737-42.