Nrf2 activator-3 (compound 24) (1 μM, 5 μM, and 10 μM) is against SNP (400 μM)-induced cell death with IC50 values of 76.86±3.54 μM, 101.59±3.34 μM, and 105.1±1.84 μM at 1 μM, 5 μM, and 10 μM, respectively in PC12 cells[1]。
Nrf2 activator-3 (1-200 μM) is against PC12 and hacat cell with IC50 values of 262.70±1.98 μM and 126.70±10.39 μM, respctively[1]。
In the acute toxicity study, Nrf2 activator-3 (compound 24) shows toxicity to the experimental mice at 1000 mg/kg, the LD50 of intraperitoneal injection is 789 mg/kg, and the 95% confidence interval was 550-1000 mg/kg in balb/c mice[1].
.In in vivo pharmacokinetic properties study, Nrf2 activator-3 (5 mg/kg; Intraperitoneal injection) shows that plasma reached a maximum (323.06 ng/mL) at 2 h. the Tmax, Cmax, AUC0-inf, F% and T1/2 values are 2 hour, 323.06 ng/mL, 2929.88 ng/mL*h, 28%, 12.75 hours respctively[1].
.Nrf2 activator-3 (5 mg/kg; .i.v.) shows Tmax, Cmax, AUC0-inf, and T1/2 values are 0.08 hours, 6911.14 ng/mL, 10182.73 ng/mL*h, and 8.26 hours respctively[1].
.Nrf2 activator-3 (3 mg/kg; 10 mg/kg;30 mg/kg) reduces the cerebral infarction volume and leads to decreased neurological deficits in MCAO rats[1].
References:
[1]. Yaoqiang Lao, et al. Synthesis and biological evaluation of 1,2,4-triazole derivatives as potential Nrf2 activators for the treatment of cerebral ischemic injury. Eur J Med Chem. 2022 Jun 5;236:114315.