SH-42 is an inhibitor of ?24-dehydrocholesterol reductase (DHCR24; IC50 = 4.2 nM).1 It increases serum levels of desmosterol , the immediate precursor of cholesterol in the Bloch pathway, in mice when administered at a dose of 0.5 mg/animal per day. SH-42 increases levels of arachidonic acid and its metabolite prostaglandin E2 , as well as docosahexaenoic acid and its metabolites 19,20-EpDPA and 19,20-DiHDPA, in the peritoneal lavage fluid in a mouse model of peritonitis induced by zymosan A .2
1.Müller, C., Hemmers, S., Bartl, N., et al.New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductaseEur. J. Med. Chem.140305-320(2017)
2.K?rner, A., Zhou, E., Müller, C., et al.Inhibition of δ24-dehydrocholesterol reductase activates pro-resolving lipid mediator biosynthesis and inflammation resolutionProc. Natl. Acad. Sci. USA116(41)20623-20634(2019)
