AA147

AA147 is a endoplasmic reticulum (ER) proteostasis regulator. AA147 promotes protection against oxidative damage in neuronal cells and prevents endothelial barrier dysfunction by activating ATF6 arm (selectively) of the unfolded protein response (UPR) and the NRF2 oxidative stress response. AA147 can rebalances XBP1s expression in vivo, and also induces survival motor neuron (SMN) expression and spinal motorneuron (MN) protection^[1][2][3][4]. In Vitro: AA147 (20-0.078 μM (dilution in half); 6 or 16 h) protects against glutamate-induced oxidative toxicity in HT22 cells by decreasing the reactive oxygen species (ROS)-associated damage^[1].
AA147 (10 μM; 16 h) induces NRF2-dependent upregulation of oxidative stress response genes in HT22 cells^[1].
AA147 (10 μM; 16 h) covalently modifies KEAP1 to promote NRF2 activation in HT22 cells^[1].
AA147 (5, 10, 15 μM; 4, 8, 16, 24, 48 h) induces ATF6 activation and upregulates phosphorylation of cofilin in BPAEC^[2].
AA147 (10 μM; 24 h) reduces LPS-induced endothelial barrier disruption in BPAEC^[2].
AA147 (5, 10 μM; 135 h) enhances lung endothelial barrier integrity^[2]. In Vivo: AA147 (intrathecal injection; single for 3 days) can rebalance XBP1s expression in severe SMA-like mice by activating ATF6, and also induce survival motor neuron expression and spinal motorneuron protection^[3].