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Microsomal cytochrome P450 as a target for drug discovery and repurposing.
- Source :
-
Drug metabolism reviews [Drug Metab Rev] 2017 Feb; Vol. 49 (1), pp. 1-17. Date of Electronic Publication: 2016 Nov 22. - Publication Year :
- 2017
-
Abstract
- Cytochrome P450 (P450) enzymes are ancient electron-transfer-chain system of remarkable biological importance. Microsomal P450 enzymes are the P450 attached to endoplasmic reticulum, which, in humans, are critical for body's defenses against xenobiotics by mediating their metabolism, and cell signaling by mediating arachidonic acid (AA) transformation to several potent bioactive molecules. Only recently, modulating P450-mediated AA metabolism has risen as a promising new drug target. This review presents the therapeutic potential of finding effective, selective and safe treatments targeting P450-mediated AA metabolism, and the several approaches that have been used to find these treatments; among which, our focus was on modulators of P450 activities. We detailed the efforts done to develop new molecular entities designed to modulate P450, and the more recent efforts tried to employ our previous knowledge on drug metabolism to repurpose old drugs with the capacity to alter P450-mediated drug metabolism to target AA metabolism. Because of the long recognition of P450 role in xenobiotic metabolism, several clinically approved agents were identified to alter P450 activity. Repurposing old drugs as P450 modulators can facilitate bringing treatments targeting P450-mediated AA metabolism to clinical trials. However, the capacity of the modulation of P450-derived AA metabolites of clinically approved drugs has to be systematically investigated and validated for their new use in humans.
- Subjects :
- Arachidonic Acid metabolism
Arachidonic Acid physiology
Cytochrome P-450 Enzyme Inducers pharmacology
Cytochrome P-450 Enzyme Inhibitors pharmacology
Cytochrome P-450 Enzyme System metabolism
Cytochrome P-450 Enzyme System physiology
Drug Interactions
Epoxide Hydrolases antagonists & inhibitors
Humans
Cytochrome P-450 Enzyme System drug effects
Drug Discovery
Drug Repositioning
Microsomes enzymology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-9883
- Volume :
- 49
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Drug metabolism reviews
- Publication Type :
- Academic Journal
- Accession number :
- 27819488
- Full Text :
- https://doi.org/10.1080/03602532.2016.1257021