S1R agonist 1 (Compound 6b) is a selective S1R agonist with Kis of 0.93 nM and 72 nM for S1R and S2R, respectively. S1R agonist 1 exhibits neuroprotection against ROS and NMDA-induced neurotoxicity.
S1R agonist 1 (Compound 6b; 0.1-5 μM) significantly increases the nerve growth factor (NGF) induced neurite outgrowth at all the tested concentrations in a dose-dependent manner in PC12 cell lines[1].S1R agonist 1 (24 h) significantly prevents cell damage induced by Rotenone when tested at the concentration of 1 μM in SHSY5Y cells[1].S1R agonist 1 (0.1-5 μM; 24 h) demonstrates a neuroprotective effect against NMDA stimuli in SHSY5Y cells[1].S1R agonist 1 (0-10 μM; 24-72 h) shows no cytotoxicity against A549, LoVo and Panc-1 cells[1].
S1R agonist 1 (Compound 6b; 0.1-50 μM; 120 h) induces the death of 4 Zebrafish embryos out of 8 at 10 μM[1].
References:
[1]. Linciano P, et al. Novel S1R agonists counteracting NMDA excitotoxicity and oxidative stress: A step forward in the discovery of neuroprotective agents. Eur J Med Chem. 2023 Mar 5;249:115163.