The in vivo oxidation of arachidonic acid produces a multitude of compounds which have been found to act as modulators of vascular physiology. Arachidonic acid epoxides (EETs), endogenous regulators of blood pressure and vascular inflammation, are hydrolyzed by the soluble epoxide hydrolase (sEH). Preliminary evidence suggests that sEH inhibition by acyclic urea compounds drastically attenuates urinary albumin excretion (UAE) in Zucker rat models. These inhibitors however are difficult to formulate due to their poor solubility. In addition, the current absorption based in vitro assays cannot distinguish between those inhibitors with the highest potency. Therefore, it is hypothesized that 1) fluorescent substrates will increase the sensitivity of the current enzymatic inhibitor assay and 2) heterocyclic compounds are potent inhibitors of sEH with improved physical properties. These hypotheses will be tested using the following specific aims:
Specific Aim I : Test the hypothesis that a fluorescent based kinetic assay for sEH activity provides a highly sensitive platform for the rapid, high-throughput evaluation of inhibitors.
Specific Aim II : Test the hypothesis that inhibitors, which have reduced rotational freedom within the primary pharmacophore, are potent inhibitors of sEH with increase water solubility.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL078096-01
Application #
6835494
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Schucker, Beth
Project Start
2004-09-01
Project End
2006-08-31
Budget Start
2004-09-01
Budget End
2005-08-31
Support Year
1
Fiscal Year
2004
Total Cost
$42,976
Indirect Cost
Name
University of California Davis
Department
Zoology
Type
Schools of Earth Sciences/Natur
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
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