Identification of potent inhibitors of the chicken soluble epoxide hydrolase.

Authors :: Shihadih DS
Harris TR
Yang J
Merzlikin O
Lee KS
Hammock BD
Morisseau C
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Jan 15; Vol. 25 (2), pp. 276-9. Date of Electronic Publication: 2014 Nov 26.
Publication Year :: 2015
Abstract: In vertebrates, soluble epoxide hydrolase (sEH) hydrolyzes natural epoxy-fatty acids (EpFAs), which are chemical mediators modulating inflammation, pain, and angiogenesis. Chick embryos are used to study angiogenesis, particularly its role in cardiovascular biology and pathology. To find potent and bio-stable inhibitors of the chicken sEH (chxEH) a library of human sEH inhibitors was screened. Derivatives of 1(adamantan-1-yl)-3-(trans-4-phenoxycyclohexyl) urea were found to be very potent tight binding inhibitors (KI <150pM) of chxEH while being relatively stable in chicken liver microsomes, suggesting their usefulness to study the role of EpFAs in chickens.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)