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Exploring CYP2J2: Lipid mediators, inhibitors and therapeutic implications

: Sisignano, M.; Steinhilber, D.; Parnham, M.J.; Geisslinger, G.


Drug Discovery Today 25 (2020), No.9, pp.1744-1753
ISSN: 1359-6446
ISSN: 1878-5832
Journal Article
Fraunhofer IME ()

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.