SH-42

SH-42 is an inhibitor of ∆²⁴-dehydrocholesterol reductase (DHCR24; IC₅₀ = 4.2 nM).¹ It increases serum levels of desmosterol (24-dehydro cholesterol; Item No. 14943), the immediate precursor of cholesterol (Item No. 9003100) 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 (Item Nos. 90010 | 90010.1 | 10006607) and its metabolite prostaglandin E₂ (PGE₂; Item No. 14010), as well as docosahexaenoic acid (Item No. 90310) 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 (Item No. 21175).² SH-42 (0.5 mg/animal three times per week) decreases disease severity in mice expressing liver X receptor α (LXRα-positive) but not LXRα-deficient mice in a model of hepatic steatosis induced by a high-fat high-cholesterol diet.³

WARNING This product is not for human or veterinary use.

1. Müller, C., Hemmers, S., Bartl, N., et al. New chemotype of selective and potent inhibitors of human delta 24-dehydrocholesterol reductase. Eur. J. Med. Chem. 140, 305-320 (2017).

2. Körner, A., Zhou, E., Müller, C., et al. Inhibition of Δ24-dehydrocholesterol reductase activates pro-resolving lipid mediator biosynthesis and inflammation resolution. Proc. Natl. Acad. Sci. USA 116(41), 20623-20634 (2019).

3. Zhou, E., Ge, X., Nakashima, H., et al. Inhibition of DHCR24 activates LXRα to ameliorate hepatic steatosis and inflammation. EMBO Mol. Med. e16845 (2023).