Keap1/Nrf2/ARE activator 2 is an activator of the Keap1/Nrf2/ARE pathway, acting as a non-competitive inhibitor of AChE with an IC50 of 14.79 μM and a Ki of 1.35 μM. It enhances Nrf2 nuclear translocation, thereby upregulating antioxidant gene expression and boosting cellular defenses against oxidative stress. In PC12 cells, Keap1/Nrf2/ARE activator 2 demonstrates significant neuroprotective effects against damage induced by H2O2 and Scopolamine (SCA). In zebrafish models, it alleviates cognitive deficits and neuroinflammation associated with SCA-induced impairments. This compound is relevant for Alzheimer's disease research.

Keap1/Nrf2/ARE activator 2 (compound 32), when applied at concentrations up to 20 μM for 24 hours, shows no significant toxicity to PC12 cells. At concentrations of 5-20 µM over the same duration, it exhibits notable cytoprotective effects against H₂O₂ and SCA-induced damage in PC12 cells, leading to increased cell viability, reduced LDH and ROS release, and inhibition of apoptosis. Furthermore, at 20 µM, it induces time-dependent accumulation and nuclear translocation of Nrf2 in PC12 cells over 2-8 hours. Additionally, exposure to 20 µM for 6-24 hours upregulates various antioxidant systems in PC12 cells, including HO-1, NQO1, Trx, TrxR, and GCLC mRNA.

The Keap1/Nrf2/ARE activator 2 (5 μM, 48 hours) enhances cognitive function in a zebrafish model induced by SCA by reducing neuroinflammation, restoring cholinergic function, and activating the Nrf2/ARE antioxidant pathway.