CUDA

Epoxyeicosatrienoic acid (EpETrE; EET) metabolites of arachidonic acid such as 11(12)-EET and 14(15)-EET have been identified as endothelium derived hyperpolarizing factors with vasodilator activity.¹ Soluble epoxide hydrolase (sEH) catalyzes the conversion of EETs to the corresponding dihydroxy eicosatrienoic acids (DiHETrEs; DHETs) thereby diminishing their activity. CUDA is an inhibitor of sEH exhibiting IC₅₀ values of 11.1 nM and 112 nM for the mouse and human enzymes, respectively.² In COS-7 cells, 10 µM CUDA blocks conversion of 1 µM 14,15-EET to 14,15-DHET by 94%. CUDA activates peroxisome proliferator-activated receptor α (PPARα) 8-fold at a concentration of 10 µM but exhibits no affect on PPARδ or PPARγ³

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1. Fleming, I. Cytochrome P450 epoxygenases as EDHF synthase(s). Pharmacol. Res. 49(6), 525-533 (2004).

2. Morisseau, C., Goodrow, M.H., Newman, J.W., et al. Structural refinement of inhibitors of urea-based soluble epoxide hydrolases. Biochem. Pharmacol. 63(9), 1599-1608 (2002).

3. Fang, X., Hu, S., Watanabe, T., et al. Activation of peroxisome proliferator-activated receptor α by substituted urea-derived soluble epoxide hydrolase inhibitors. J. Pharmacol. Exp. Ther. 314(1), 260-270 (2005).

Isobe, Y., Itagaki, M., ito, Y., et al. Comprehensive analysis of the mouse cytochrome P450 family responsible for omega-3 epoxidation of eicosapentaenoic acid. Sci. Rep. 8(1), 7954 (2018).

Gouveia-Figueira, S., Karlsson, J., Deplano, A., et al. Characterisation of (R)-2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide as a dual fatty acid amide hydrolase: Cyclooxygenase inhibitor. PLoS One 10(9), e0139212 (2015).