Description
20-
HETE is an important metabolite of arachidonic acid in the vasculature, especially in the kidney, where it is synthesized by cytochrome P450 (CYP450) enzymes of the 4A family.
1,2 Alkylaryl imidazoles have been shown to inhibit certain CYP450 enzymes, including the CYP4A enzymes associated with 20-
HETE synthesis.
3 CAY10462 is the hydrochloride salt of CAY10434 and selective inhibitor of the 20-
HETE synthase CYP4A11 exhibiting an IC
50 of 8.8 nM when tested in human renal microsomes.
4 CAY10434 is nearly 200 times less potent as an inhibitor of 1A, 1C, and 3A CYP450 enzymes.
References
1. Harder, D.R., Lange, A.R., Gebremedhin, D., et al. Cytochrome P450 metabolites of arachidonic acid as intracellular signaling molecules in vascular tissue J. Vasc. Res. 34,237-243(1997).
2. Imig, J.D., Zou, A.P., Stec, D.E., et al. Formation and actions of 20-hydroxyeicosatetraenoic acid in rat renal arterioles Am. J. Physiol. 270,R217-R227(1996).
3. Nakamura, T., Kakinuma, H., Umemiya, H., et al. Imidazole derivatives as new potent and selective 20-HETE synthase inhibitor Bioorg. Med. Chem. Lett. 14,333-336(2004).
