Exploring CYP2J2: lipid mediators, inhibitors and therapeutic implications

•CYP2J2 synthesizes epoxylipids that act as potent signaling mediators•A role for these lipids has been suggested for pain, angiogenesis and tumor growth•Several CYP2J2-inhibitors have been identified – among them already approved drugs•Inhibiting CYP2J2 may introduce novel therapeutic options for p...

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Bibliographic Details
Published in:Drug discovery today 2020-09, Vol.25 (9), p.1744-1753
Main Authors: Sisignano, Marco, Steinhilber, Dieter, Parnham, Michael J., Geisslinger, Gerd
Format: Article
Language:English
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Summary:•CYP2J2 synthesizes epoxylipids that act as potent signaling mediators•A role for these lipids has been suggested for pain, angiogenesis and tumor growth•Several CYP2J2-inhibitors have been identified – among them already approved drugs•Inhibiting CYP2J2 may introduce novel therapeutic options for pain and tumor growth In contrast to other drug-metabolizing cytochrome P450 (CYP) oxygenases, CYP2J2 shows considerable extrahepatic activity and is responsible for the olefin epoxidation of several polyunsaturated fatty acid (PUFA) precursors. The resulting epoxylipids act as signaling mediators and show a remarkable variety of biological functions. Recent studies suggest a role of selected CYP2J2-derived epoxylipids and their metabolites in chronic pain, as well as angiogenesis, hematopoiesis, metabolic disorders, and tumor growth. These pleiotropic effects of CYP products imply that targeting CYP2J2 could represent a novel therapeutic strategy in these fields. Here, we explore the biological functions of CYP2J2-derived epoxylipids and discuss therapeutic implications of the CYP2J2 inhibitors that are known so far.
ISSN:1359-6446
1878-5832
DOI:10.1016/j.drudis.2020.07.002