The 2014 Bernard B. Brodie award lecture-epoxide hydrolases: drug metabolism to therapeutics for chronic pain

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Sean Kodani, Bruce D Hammock

Abstract

Dr. Bernard Brodie's legacy is built on fundamental discoveries in pharmacology and drug metabolism that were then translated to the clinic to improve patient care. Similarly, the development of a novel class of therapeutics termed the soluble epoxide hydrolase (sEH) inhibitors was originally spurred by fundamental research exploring the biochemistry and physiology of the sEH. Here, we present an overview of the history and current state of research on epoxide hydrolases, specifically focusing on sEHs. In doing so, we start with the translational project studying the metabolism of the insect juvenile hormone mimic R-20458 [(E)-6,7-epoxy-1-(4-ethylphenoxy)-3,7-dimethyl-2-octene], which led to the identification of the mammalian sEH. Further investigation of this enzyme and its substrates, including the epoxyeicosatrienoic acids, led to insight into mechanisms of inflammation, chronic and neuropathic pain, angiogenesis, and other physiologic processes. This basic knowledge in turn led to the development of potent inhibitors of the sEH that are promising therapeutics for pain, hypertension, chronic obstructive pulmonary disorder, arthritis, and other disorders.

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Citations

Nov 3, 2015·Toxicology and Applied Pharmacology·Sumanta Kumar GoswamiBruce D Hammock
Aug 1, 2015·Analytical and Bioanalytical Chemistry·Yongliang CuiBruce D Hammock
Mar 19, 2016·The Journal of Pharmacology and Experimental Therapeutics·Sumanta Kumar GoswamiBruce D Hammock
May 27, 2016·Proceedings of the National Academy of Sciences of the United States of America·Derek W GilroyDavid Bishop-Bailey
Jun 28, 2016·The Journal of Steroid Biochemistry and Molecular Biology·Florence DalencSandrine Silvente-Poirot
Jun 4, 2016·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Xue-Qing LiLars Weidolf
Oct 5, 2017·Archives of Toxicology·Anne MarowskyMichael Arand
Jun 1, 2018·Journal of Periodontal Research·M H NapimogaB D Hammock
Apr 22, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Zhican WangZhengping Wang
Apr 20, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Milan FialaMatteo Pellegrini
Aug 6, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Chiara BrulloOlga Bruno
Jul 23, 2020·British Journal of Pharmacology·Philippe de MedinaMarc Poirot
Aug 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Anna FishbeinDipak Panigrahy
Oct 21, 2020·Journal of Clinical Pharmacology·Guohua AnBruce D Hammock
Dec 16, 2019·Prostaglandins & Other Lipid Mediators·Malvina Hoxha, Bruno Zappacosta
Jan 28, 2021·Psychoneuroendocrinology·Natasha Z AnitaWalter Swardfager
Feb 5, 2019·Biochimie·Sean D Kodani, Christophe Morisseau
Apr 20, 2021·Frontiers in Physiology·Cindy B McReynoldsJun Yang
Mar 14, 2020·Journal of Chemical Theory and Computation·Nathan M LimDavid L Mobley
Jul 11, 2020·The American Journal of Pathology·Bruce D HammockDipak Panigrahy
Oct 12, 2021·The Proceedings of the Nutrition Society·Rasha N M Saleh, Anne Marie Minihane

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