title: Identification of potent inhibitors of the chicken soluble epoxide hydrolase.
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.
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Diyala S
authors.initials: DS
authors.lastname: Shihadih
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Todd R
authors.initials: TR
authors.lastname: Harris
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Oleg
authors.initials: O
authors.lastname: Merzlikin
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Kin Sing S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Department of Entomology and Nematology, U.C. Davis Comprehensive Cancer Center, University of California, Davis, Davis, CA 95616, USA. Electronic address: chmorisseau@ucdavis.edu.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
mesh_terms: D000818:Animals; D002645:Chickens; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D004851:Epoxide Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D014508:Urea; D004851:Epoxide Hydrolases
keywords: Angiogenesis; Di-substituted ureas; Epoxy-eicosatrienoic acids; High throughput screening; Liver microsomes