ReviewNature reviews. Drug discovery2011
Managing the challenge of chemically reactive metabolites in drug development.
Review in Nature reviews. Drug discovery, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
120 citing papers in PubMed, 450 citations in OpenAlex.
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- Omeprazole activation of CD4+ and CD8+ T-cells through off-target covalent modification of cellular proteins.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- In Silico Drug Design and Discovery: Big Data for Small Molecule Design-2nd Edition.Biomolecules · 2026Article
- Normalizing Covalent Potency for Electrophilicity with Ligand Reactivity Efficiency.Journal of medicinal chemistry · 2026Review
- Synthesis and Antitumor Potency of 2International journal of molecular sciences · 2026Article
- Article
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- Unveiling the metabolic fate of drugs through metabolic reaction-based molecular networking.Acta pharmaceutica Sinica. B · 2025Article
- Use of new approach methodology for hepatic safety assessment of covalent inhibitor drug candidates.Toxicology research · 2025Article
- Article
- Current hPSC-derived liver organoids for toxicity testing: Cytochrome P450 enzymes and drug metabolism.Toxicological research · 2025Review
- Covalent-Allosteric Inhibitors: Do We Get the Best of Both Worlds?Journal of medicinal chemistry · 2025Review
- Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury.Archives of toxicology · 2025Review
- Unraveling the Role of CYP2E1 in Antitubercular Drug-Induced Hepatotoxicity: From Molecular Mechanisms to Clinical Implications.International journal of hepatology · 2025Review
- iDILI-MT: identifying drug-induced liver injury compounds with a multi-head Transformer.PeerJ. Computer science · 2025Article
- AI Promoted Virtual Screening, Structure-Based Hit Optimization, and Synthesis of Novel COVID-19 S-RBD Domain Inhibitors.Journal of chemical information and modeling · 2024Article
- Detection and Quantification of Drug-Protein Adducts in Human Liver.Journal of proteome research · 2024Article
- Drug hypersensitivity reactions: review of the state of the science for prediction and diagnosis.Toxicological sciences : an official journal of the Society of Toxicology · 2024Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 12 institutions in 5 countries.
Funding
Abstract
The normal metabolism of drugs can generate metabolites that have intrinsic chemical reactivity towards cellular molecules, and therefore have the potential to alter biological function and initiate serious adverse drug reactions. Here, we present an assessment of the current approaches used for the evaluation of chemically reactive metabolites. We also describe how these approaches are being used within the pharmaceutical industry to assess and minimize the potential of drug candidates to cause toxicity. At early stages of drug discovery, iteration between medicinal chemistry and drug metabolism can eliminate perceived reactive metabolite-mediated chemical liabilities without compromising pharmacological activity or the need for extensive safety evaluation beyond standard practices. In the future, reactive metabolite evaluation may also be useful during clinical development for improving clinical risk assessment and risk management. Currently, there remains a huge gap in our understanding of the basic mechanisms that underlie chemical stress-mediated adverse reactions in humans. This review summarizes our views on this complex topic, and includes insights into practices considered by the pharmaceutical industry.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.