Ceapin-A7 (2323027-38-7) is a selective inhibitor (IC50 = 590 nM) of transcription factor ATF6a, one of the three branches of the unfolded protein response.1 It inhibits activation of ATF6α in response to ER stress without inhibiting ER-bound transcription factors ATF6b or SREBP or the IRE1 or PERK branches of the UPR. Ceapin-A7 also show no toxicity to unstressed cells. It induces neomorphic association of the ER and peroxisomes by directly tethering the cytosolic domain of ATF6a to the peroxisomal transporter ABCD3 without inhibiting its transporter activity.2 See companion activator 10-3973.
- Gallagher et al. (2016), Ceapins are a new class of unfolded protein response inhibitors, selectively targeting the ATF6α branch; eLife 5 e11878
- Torres et al. (2019), Ceapins block the unfolded protein response sensor ATF6α by inducing a neomorphic inter-organelle tether; eLife 8 e46595