Identification of potent inhibitors of the chicken soluble epoxide hydrolase

Diyala S. Shihadih, Todd R. Harris, Jun Yang, Oleg Merzlikin, Kin Sing S Lee, Bruce D. Hammock, Christophe Morisseau

Research output: Contribution to journalArticle

2 Scopus citations

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 <150 pM) of chxEH while being relatively stable in chicken liver microsomes, suggesting their usefulness to study the role of EpFAs in chickens.

Original languageEnglish (US)
Pages (from-to)276-279
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number2
DOIs
StatePublished - Jan 15 2015

Keywords

  • Angiogenesis
  • Di-substituted ureas
  • Epoxy-eicosatrienoic acids
  • High throughput screening
  • Liver microsomes

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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  • Cite this

    Shihadih, D. S., Harris, T. R., Yang, J., Merzlikin, O., Lee, K. S. S., Hammock, B. D., & Morisseau, C. (2015). Identification of potent inhibitors of the chicken soluble epoxide hydrolase. Bioorganic and Medicinal Chemistry Letters, 25(2), 276-279. https://doi.org/10.1016/j.bmcl.2014.11.053