ArticleBritish journal of pharmacology2012
Metabolic map and bioactivation of the anti-tumour drug noscapine.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- A Systematic Review of Drug Metabolism Studies of Plants With Anticancer Properties: Approaches Applied and Limitations.European journal of drug metabolism and pharmacokinetics · 2020Pooled it
- A Semi-Mechanistic Population Pharmacokinetic Model of Noscapine in Healthy Subjects Considering Hepatic First-Pass Extraction and CYP2C9 Genotypes.Drugs in R&D · 2024Trial
- CYP3A-Mediated Carbon-Carbon Bond Cleavages in Drug Metabolism.Biomolecules · 2024Review
- Anticancer Activity of Region B Capsaicin Analogs.Journal of medicinal chemistry · 2023Review
- Metabolic Profile of C-Prenyl Coumarins Using Mass Spectrometry-Based Metabolomics.Molecules (Basel, Switzerland) · 2021Article
- Metabolic map of the antiviral drug podophyllotoxin provides insights into hepatotoxicity.Xenobiotica; the fate of foreign compounds in biological systems · 2021Article
- Nontargeted Metabolomics by High-Resolution Mass Spectrometry to Study the In Vitro Metabolism of a Dual Inverse Agonist of Estrogen-Related Receptors β and γ, DN203368.Pharmaceutics · 2021Article
- Inhibitory Effects ofPharmaceutics · 2021Article
- Production of metabolites of the anti-cancer drug noscapine using a P450Biotechnology reports (Amsterdam, Netherlands) · 2019Article
- Noscapine, a Non-addictive Opioid and Microtubule-Inhibitor in Potential Treatment of Glioblastoma.Neurochemical research · 2019Review
- A metabolomic perspective of pazopanib-induced acute hepatotoxicity in mice.Xenobiotica; the fate of foreign compounds in biological systems · 2019Article
- Application of Metabolomics in the Study of Natural Products.Natural products and bioprospecting · 2018Article
- Update of the Scientific Opinion on opium alkaloids in poppy seeds.EFSA journal. European Food Safety Authority · 2018Article
- Metabolic map of osthole and its effect on lipids.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Revisiting the Metabolism and Bioactivation of Ketoconazole in Human and Mouse Using Liquid Chromatography-Mass Spectrometry-Based Metabolomics.International journal of molecular sciences · 2017Article
- Metabolism profiling of amino-noscapine.European journal of drug metabolism and pharmacokinetics · 2016Article
- Metabolic pathway profiling of the derivative of important herbal component noscapine.European journal of drug metabolism and pharmacokinetics · 2016Article
- Formulation, Pharmacokinetic, and Efficacy Studies of Mannosylated Self-Emulsifying Solid Dispersions of Noscapine.PloS one · 2016Article
- Noscapine recirculates enterohepatically and induces self-clearance.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2015Article
- Metabolic mapping of A3 adenosine receptor agonist MRS5980.Biochemical pharmacology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNoscapine is a promising anti-tumour agent. The purpose of the present study was to describe the metabolic map and investigate the bioactivation of noscapine. EXPERIMENTAL APPROACH: Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry-based metabolomics was used to analyse the in vitro incubation mixtures, urine and faeces samples from mice treated with noscapine. Recombinant drug-metabolizing enzymes were employed to identify those involved in noscapine metabolism. Hepatic GSH levels and serum biochemistry were also carried out to determine reactive metabolites of noscapine. KEY
resultsSeveral novel phase I metabolites of noscapine were detected after oral gavage of mice, including an N-demethylated metabolite, two hydroxylated metabolites, one metabolite undergoing both demethylation and cleavage of the methylenedioxy group and a bis-demethylated metabolite. Additionally, several novel glucuronides were detected, and their structures were elucidated through MS/MS fragmentology. Recombinant enzymes screening showed the involvement of several cytochromes P450, flavin-containing mono-oxygenase 1 and the UDP-glucuronosyltransferases UGT1A1, UGT1A3, UGT1A9 and UGT2B7, in noscapine metabolism. In vitro glutathione trapping revealed the existence of an ortho-quinone reactive intermediate formed through further oxidation of a catechol metabolite. However, this bioactivation process of noscapine does not occur in vivo. Similar to this result, altered glutathione levels in liver and serum biochemistry revealed no evidence of hepatic damage, thus indicating that, at least in mice, noscapine does not induce hepatotoxicity through bioactivation. CONCLUSIONS AND IMPLICATIONS: A comprehensive metabolic map and bioactivation evaluation provides important information for the development of noscapine as an anti-tumour drug.
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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.