ArticleACS medicinal chemistry letters2012
Identification of the Significant Involvement and Mechanistic Role of CYP3A4/5 in Clopidogrel Bioactivation.
Article in ACS medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- Pharmacometabolomics Detects Unreported Clopidogrel Metabolites in the Urine of Kidney and Liver Transplant Recipients.Metabolites · 2026Article
- Pleiotropic effects of clopidogrel.Purinergic signalling · 2022Review
- Cytochrome P450 enzyme-mediated auto-enhanced photodynamic cancer therapy of co-nanoassembly between clopidogrel and photosensitizer.Theranostics · 2020Article
- DT-678 inhibits platelet activation with lower tendency for bleeding compared to existing P2YPharmacology research & perspectives · 2019Article
- Significant Improvement of Antithrombotic Responses to Clopidogrel by Use of a Novel Conjugate as Revealed in an Arterial Model of Thrombosis.The Journal of pharmacology and experimental therapeutics · 2016Article
- Cytochrome allelic variants and clopidogrel metabolism in cardiovascular diseases therapy.Molecular biology reports · 2016Review
- Dosing Recommendations for Concomitant Medications During 3D Anti-HCV Therapy.Clinical pharmacokinetics · 2016Review
- Harnessing C-H Borylation/Deborylation for Selective Deuteration, Synthesis of Boronate Esters, and Late Stage Functionalization.The Journal of organic chemistry · 2015Article
- Comparative risk of ischemic stroke among users of clopidogrel together with individual proton pump inhibitors.Stroke · 2015Article
- Contributions of intestine and plasma to the presystemic bioconversion of vicagrel, an acetate of clopidogrel.Pharmaceutical research · 2014Article
- Deuterated clopidogrel analogues as a new generation of antiplatelet agents.ACS medicinal chemistry letters · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical response to the antiplatelet prodrug clopidogrel is associated with high intersubject variability and a certain level of therapeutic resistance. Previous studies have suggested that genetic polymorphism of CYP2C19 might be one determinant of clopidogrel efficacy and led to the CYP2C19 genotype-tailored antithrombotic therapy. However, evidence against the role of CYP2C19 from multiple studies implied the involvement of other factors. Here, we report that prodrug activation of the thiophene motif in clopidogrel is attenuated by heavy metabolic attrition of the piperidine motif. CYP3A4/5 was identified to be the enzyme metabolizing the piperidine motif. Inhibiting CYP3A4/5-mediated attrition was shown to potentiate active metabolite formation, which was found to be catalyzed by multiple CYP enzymes. Identifying the significant involvement of CYP3A4/5 and characterizing its mechanistic role in clopidogrel bioactivation might assist future pharmacogenomic studies in exploring the full mechanism underlying clopidogrel efficacy.
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