NK-252 is a potential activator of Nrf2. It has great Nrf2-activating potential.

NK-252 shows this effect with higher potency than OPZ based on the fact that the EC2 value (concentration for a 2-fold induction above background), calculated with linear extrapolation from the values above and below the induction threshold, is 20.8 μM for OPZ and 1.36 μM for NK-252. NK-252 has potential as an Nrf2 activator in hepatic cells. The protective effects of OPZ and NK-252 are examined against H2O2-induced cytotoxicity using Huh-7 cells to evaluate their antioxidant properties. The cells treated with OPZ or NK-252 show increased resistance to H2O2-induced cytotoxicity compared with control cells. The luciferase activity in Huh-7.5 cells treated with Oltipraz (OPZ) or NK-252 displays activation of the NAD(P)H quinone oxidoreductase 1 (NQO1)-ARE in a dose-dependent manner. Prototypical Nrf2 activators that include OPZ have been reported to protect microglial cells from H2O2-induced cytotoxicity [1].

Rats on a choline-deficient L-amino acid–defined (CDAA) diet that received OPZ or NK-252 exhibited decreased liver fibrosis scores compared to those on the same diet without these compounds. NK-252’s impact on fibrosis was dose-dependent[1]. CDAA diet-fed rats showed a nearly 20-fold increase in liver fibrosis area compared to rats on a normal diet (naive), which was significantly reduced by treatments (5.80% for OPZ, 6.20% for NK-252_low, and 4.97% for NK-252_high). Although NK-252 did not show antitumor effects in P388/S- and P388/VCR-mice when used alone, its combination with Etoposide notably enhanced the lifespan of mice with P388/VCR cancer, more than Etoposide alone[2]. Similarly, oral administration of NK-252 with Etoposide significantly prolonged the lifespan of P388/S inoculated mice, showing an improved therapeutic outcome compared to using Etoposide by itself.