Description
BHPI is a potent inhibitor of nuclear estrogen-ERalpha-regulated gene expression. Elicits sustained ERalpha-dependent activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), and persistent inhibition of protein synthesis. IC50 value: Target: ERalpha inhibitor BHPI is effective because it elicits sustained ERalpha-dependent activation of the endoplasmic reticulum (EnR) stress sensor, the unfolded protein response (UPR), and persistent inhibition of protein synthesis. In ERalpha(+) cancer cells, BHPI rapidly hyperactivates plasma membrane PLCgamma, generating inositol 1,4,5-triphosphate (IP3), which opens EnR IP3R calcium channels, rapidly depleting EnR Ca(2+) stores. BHPI distorts a newly described action of estrogen-ERalpha: mild and transient UPR activation. In contrast, BHPI elicits massive and sustained UPR activation, converting the UPR from protective to toxic