Description
NK 252 is a Nrf2 activator that interacts directly with the domain containing the Nrf2-binding site of Keap1. At 1.36 μM, it is reported to activate the NQO1-antioxidant response element in a luciferase reporter gene assay two-fold above background. NK 252 has been shown to downregulate the expression of fibrogenic genes, producing antifibrotic effects in a rat model of non-alcoholic steatohepatitis.
in vivo
Rats on a choline-deficient L-amino acid–defined (CDAA) diet given OPZ or NK-252 display decreased fibrosis scores compared with CDAA control rats, with median scores of 3, corresponding to bridging fibrosis. CDAA control rats display approximately 20-fold augmentation of the liver fibrosis area compared with rats fed a normal control diet (naive) (14.7 and 0.72%, respectively).This augmentation is also drastically reduced by administration of OPZ or NK-252 (5.80% for OPZ, 6.20% for NK-252_low, and 4.97% for NK-252_high). The effects of NK-252 on both fibrosis score and fibrosis area are dose-dependent[1]. NK-252 alone has no antitumour effect in P388/S- and P388/VCR-mice. The combination therapy of Etoposide with NK-252 administered p.o. significantly increases the life-span of mice inoculated i.p. with P388/S compared with the corresponding therapeutic effects with Etoposide alone. The combination therapy with Etoposide and NK-252 significantly increases the life-span of mice inoculated i.p. with P388/VCR compared with the corresponding survival time with Etoposide alone[2].
References
[1]. shimozono r, asaoka y, yoshizawa y, et al. nrf2 activators attenuate the progression of nonalcoholic steatohepatitis-related fibrosis in a dietary rat model. mol pharmacol. 2013 jul;84(1):62-70.
[2]. kiue a, sano t, naito a, et al. reversal by two dihydropyridine compounds of resistance to multiple anticancer agents in mouse p388 leukemia in vivo and in vitro. jpn j cancer res. 1990 oct;81(10):1057-64.