ArticleJournal of chemical information and modeling2022
Unraveling the Abnormal Molecular Mechanism of Suicide Inhibition of Cytochrome P450 3A4.
Article in Journal of chemical information and modeling, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 3 citations in OpenAlex.
- Kinetic Analysis of Irreversible Covalent Enzyme Inhibitors and Its Use in Drug Design.International journal of molecular sciences · 2026Review
- Multi-task molecular representation learning based on soft prompting of the important subgraph.Molecular genetics and genomics : MGG · 2026Article
- The impact of the exposome on cytochrome P450-mediated drug metabolism.Frontiers in pharmacology · 2025Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suicide inhibition of the CYP3A4 enzyme by a drug inactivates the enzyme in the drug biotransformation process and often shows safety concerns about the drug. Despite extensive experimental studies, the abnormal molecular mechanism of a suicide inhibitor that forms a covalent bond with the residue far away from the catalytically active center of CYP3A4 inactivating the enzyme remains elusive. Here, the authors used molecular simulation approaches to study in detail how diquinone methide (DQR), the metabolite product of raloxifene, unbinds from CYP3A4 and inactivates the enzyme at the atomistic level. The results clearly indicate that in one of the intermediate states formed in its unbinding process, DQR covalently binds to Cys239, a residue far away from the catalytically active center of CYP3A4, and hinders the substrate from entering or leaving the enzyme. This work therefore provides an unprecedented way of clarifying the abnormal mechanism of suicide inhibition of the CYP3A4 enzyme.
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Registered trials
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