Biochem/physiol Actions

The pyrazole amide Ceapin-A7 is a potent and highly specific ER stress-induced ATF6α signaling blocker (IC₅₀ = 590 nM by HEK293T-based ERSE-luciferase reporter assay, ATF6α target transcripts GRP78/ERO1B/HERPUD1 induction IC₅₀ = 459/522/614 nM in U2OS cells; ER stress by 100 nM Thapsigargin) that does not affect IRE1 or PERK branches of the unfolded protein response (UPR), nor proteolytic processing of its close homolog ATF6β or SREBP. Ceapin-A7 sensitizes U2-OS cells to ER stress-induced death (thapsigargin EC₅₀ = 4.5/7.1 nM with/without 6 µM Ceapin-A7) without impacting the viability of unstressed cells.