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 language | English (US) |
|---|---|
| Pages (from-to) | 276-279 |
| Number of pages | 4 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 25 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 15 2015 |
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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
Cite this
Identification of potent inhibitors of the chicken soluble epoxide hydrolase. / Shihadih, Diyala S.; Harris, Todd R.; Yang, Jun; Merzlikin, Oleg; Lee, Kin Sing S; Hammock, Bruce D.; Morisseau, Christophe.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 25, No. 2, 15.01.2015, p. 276-279.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Identification of potent inhibitors of the chicken soluble epoxide hydrolase
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
Y1 - 2015/1/15
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.
AB - 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.
KW - Angiogenesis
KW - Di-substituted ureas
KW - Epoxy-eicosatrienoic acids
KW - High throughput screening
KW - Liver microsomes
UR - http://www.scopus.com/inward/record.url?scp=84922270820&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84922270820&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2014.11.053
DO - 10.1016/j.bmcl.2014.11.053
M3 - Article
C2 - 25479771
AN - SCOPUS:84949115957
VL - 25
SP - 276
EP - 279
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 2
ER -