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

doi:10.1016/j.bmcl.2014.11.053

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

Entomology

Research output: Contribution to journal › Article › peer-review

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

Original language	English (US)
Pages (from-to)	276-279
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2014.11.053
State	Published - 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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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 <150 pM) 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",

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AU - Shihadih, Diyala S.

AU - Harris, Todd R.

AU - Yang, Jun

AU - Merzlikin, Oleg

AU - Lee, Kin Sing S

AU - Hammock, Bruce D.

AU - Morisseau, Christophe

PY - 2015/1/15

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N2 - 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.

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KW - Di-substituted ureas

KW - Epoxy-eicosatrienoic acids

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Identification of potent inhibitors of the chicken soluble epoxide hydrolase

Abstract

Keywords

ASJC Scopus subject areas

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