1-(1-acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea (AR9281) as a potent, selective, and orally available soluble epoxide hydrolase inhibitor with efficacy in rodent models of hypertension and dysglycemia |
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Authors: | Anandan Sampath-Kumar Webb Heather Kay Chen Dawn Wang Yi-Xin Jim Aavula Basker R Cases Sylvaine Cheng Ying Do Zung N Mehra Upasana Tran Vinh Vincelette Jon Waszczuk Joanna White Kathy Wong Kenneth R Zhang Le-Ning Jones Paul D Hammock Bruce D Patel Dinesh V Whitcomb Randall MacIntyre D Euan Sabry James Gless Richard |
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Institution: | a Arête Therapeutics, Inc., 7000 Shoreline Court, South San Francisco, CA 94080, United States b Department of Entomology and UCD Cancer Center, One Shields Avenue, University of California, Davis, CA 95616, United States |
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Abstract: | 1-(1-Acetyl-piperidin-4-yl)-3-adamantan-1-yl-urea 14a (AR9281), a potent and selective soluble epoxide hydrolase inhibitor, was recently tested in a phase 2a clinical setting for its effectiveness in reducing blood pressure and improving insulin resistance in pre-diabetic patients. In a mouse model of diet induced obesity, AR9281 attenuated the enhanced glucose excursion following an intraperitoneal glucose tolerance test. AR9281 also attenuated the increase in blood pressure in angiotensin-II-induced hypertension in rats. These effects were dose-dependent and well correlated with inhibition of the sEH activity in whole blood, consistent with a role of sEH in the observed pharmacology in rodents. |
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Keywords: | sEH inhibitor AR9281 Efficacy DIO model AngII hypertension model Diabetes |
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