BHPI

BHPI is a potent ER? inhibitor that blocks nuclear estrogen–ER?-regulated gene expression effectively. It triggers sustained ER?-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 ER?, BHPI's mechanism involves the rapid hyperactivation of PLC? on the plasma membrane in ER? (+) 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. SIGNIFICANTLY, BHPI alters estrogen-ER?'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.