Design and Characterization of the First Selective and Potent Mechanism-Based Inhibitor of Cytochrome P450 4Z1.


Journal

Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531

Informations de publication

Date de publication:
14 05 2020
Historique:
pubmed: 18 4 2020
medline: 3 11 2020
entrez: 18 4 2020
Statut: ppublish

Résumé

Mammary-tissue-restricted cytochrome P450 4Z1 (CYP4Z1) has garnered interest for its potential role in breast cancer progression. CYP4Z1-dependent metabolism of arachidonic acid preferentially generates 14,15-epoxyeicosatrienoic acid (14,15-EET), a metabolite known to influence cellular proliferation, migration, and angiogenesis. In this study, we developed time-dependent inhibitors of CYP4Z1 designed as fatty acid mimetics linked to the bioactivatable pharmacophore, 1-aminobenzotriazole (

Identifiants

pubmed: 32302132
doi: 10.1021/acs.jmedchem.0c00101
doi:

Substances chimiques

Cytochrome P-450 Enzyme Inhibitors 0
Fatty Acids 0
Triazoles 0
Arachidonic Acid 27YG812J1I
CYP4Z1 protein, human EC 1.14.14.1
Cytochrome P450 Family 4 EC 1.14.14.1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4824-4836

Auteurs

John P Kowalski (JP)

Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington 98105, United States.

Matthew G McDonald (MG)

Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington 98105, United States.

Robert D Pelletier (RD)

Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington 98105, United States.

Helmut Hanenberg (H)

Department of Pediatrics III, University Children's Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany.

Constanze Wiek (C)

Department of Otorhinolaryngology and Head/Neck Surgery, Heinrich-Heine University, 40225 Düsseldorf, Germany.

Allan E Rettie (AE)

Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle, Washington 98105, United States.

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Classifications MeSH