19,20-EDP epoxide

(±)19(20)-EDP ethanolamide is an ω-3 endocannabinoid epoxide and cannabinoid (CB) receptor agonist (EC₅₀s = 108 and 280 nM for CB₁ and CB₂, respectively). It is produced through direct epoxygenation of docosahexaenoyl ethanolamide (DHEA; ) by cytochrome P450 (CYP) epoxygenases.^1,2 (±)19(20)-EDP ethanolamide (25 μM) reduces the viability of 143B metastatic osteosarcoma cells.² It decreases the production of IL-6 and increases the production of IL-10 when used at concentrations ranging from 2.5 to 10 μM in BV-2 microglia stimulated by LPS and decreases LPS-induced cytotoxicity when used at concentrations ranging from 5 to 10 μM. It also decreases nitrite production when used at a concentration of 7.5 μM, an effect that can be partially reversed by the CB₂ receptor antagonist AM630 and the PPARγ antagonist GW 9662 . (±)19(20)-EDP ethanolamide induces vasodilation of isolated preconstricted bovine coronary arteries (ED₅₀ = 1.9 μM) and reduces tube formation by human microvascular endothelial cells (HMVECs) in a Matrigel? assay.

1. McDougle, D.R., Watson, J.E., Abdeen, A.A., et al. Anti-inflammatory ω-3 endocannabinoid epoxides Proc. Natl. Acad. Sci. USA 114(30),E6034-E6043(2017).
2. Roy, J., Watson, J.E., Hong, I.S., et al. Antitumorigenic properties of omega-3 endocannabinoid epoxides J. Med. Chem. 61(13),5569-5579(2018).