Identification of potent inhibitors of the chicken soluble epoxide hydrolase

Bioorg Med Chem Lett. 2015 Jan 15;25(2):276-9. doi: 10.1016/j.bmcl.2014.11.053. Epub 2014 Nov 26.

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.

Keywords: Angiogenesis; Di-substituted ureas; Epoxy-eicosatrienoic acids; High throughput screening; Liver microsomes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chickens
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Epoxide Hydrolases / antagonists & inhibitors*
  • Humans
  • Microsomes, Liver / drug effects*
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*
  • Urea / pharmacology

Substances

  • Enzyme Inhibitors
  • Urea
  • Epoxide Hydrolases