E2012 has concentration-dependent inhibitory effects on cholesterol biosynthesis in primary culture of rat hepatocytes and HepG2 cells with IC 50 s of 11.0, and 15.1 nM, respectively.
体内研究
In vivo lenticular concentration of E 2012 after 13-week repeated dose with cataract was well above those where inhibition is observed in vitro. E 2012 induces cataract in the rat by inhibiting DHCR24 at the final step of cholesterol synthesis with associated elevation in desmosterol within the lens, preceded by desmosterol changes that would serve as a predictive safety biomarker for lenticular opacity.