Document Type

Journal Article

Department/Unit

Department of Chemistry

Language

English

Abstract

Extrahepatic cytochrome P450 enzymes (CYP450) are pivotal in the metabolism of endogenous substrates and xenobiotics. CYP2J2 is a major cardiac CYP450 and primarily metabolizes polyunsaturated fatty acids such as arachidonic acid to cardioactive epoxyeicosatrienoic acids. Due to its role in endobiotic metabolism, CYP2J2 has been actively studied in recent years with the focus on its biological functions in cardiac pathophysiology. Additionally, CYP2J2 metabolizes a number of xenobiotics such as astemizole and terfenadine and is potently inhibited by danazol and telmisartan. Notably, CYP2J2 is found to be upregulated in multiple cancers. Hence a number of specific CYP2J2 inhibitors have been developed and their efficacy in inhibiting tumor progression has been actively studied. CYP2J2 inhibitor such as C26 (1-[4-(vinyl)phenyl]-4-[4-(diphenyl-hydroxymethyl)-piperidinyl]-butanone hydrochloride) caused marked reduction in tumor proliferation and migration as well as promoted apoptosis in cancer cells. In this review, we discuss the role of CYP2J2 in cardiac pathophysiology and cancer therapeutics. Additionally, we provide an update on the substrates, reversible inhibitors and irreversible inhibitors of CYP2J2. Finally, we discuss the current gaps and future directions in CYP2J2 research.

Keywords

CYP2J2, Arachidonic acid, Epoxyeicosatrienoic acids, Cardiology, Oncology, Enzyme inhibition

Publication Date

7-2017

Source Publication Title

Biochemical Pharmacology

Volume

135

Start Page

12

End Page

21

Publisher

Elsevier

Peer Reviewed

1

Copyright

© 2017 Elsevier Inc. All rights reserved.

DOI

10.1016/j.bcp.2017.02.017

Link to Publisher's Edition

http://dx.doi.org/10.1016/j.bcp.2017.02.017

ISSN (print)

00062952

ISSN (electronic)

18732968

Available for download on Wednesday, August 01, 2018

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