AA147

AA147 is a synthetic small-molecule endoplasmic reticulum (ER) proteostasis regulator that was identified through high-throughput screening as a preferential activator of the activating transcription factor 6 (ATF6) arm of the unfolded protein response (UPR).[1][3][4][5][8] By undergoing metabolic activation to a reactive electrophile that covalently modifies ER-resident proteins, AA147 selectively engages ATF6 signaling independently of global ER stress, upregulating chaperones such as GRP78 and enhancing ER folding capacity while limiting protein misfolding and cell death.[4][5][6][8] In preclinical models, AA147 reduces glutamate- or ischemia/reperfusion-induced oxidative stress and ER stress, activates both ATF6 and nuclear factor E2-related factor 2 (Nrf2) pathways, and confers cytoprotection in neurons and other tissues, including improved neurological outcomes after cardiac arrest-induced cerebral ischemia/reperfusion injury in mice.[1][3][8] AA147 is widely used as a chemical biology tool compound to probe UPR signaling and proteostasis regulation but is not an approved therapeutic drug.

Other names

ATF6 activator 147ATF-6 activator 147ATF 6 activator 147N-(2-hydroxy-5-methylphenyl)benzenepropanamide