ArticleThe Journal of pharmacology and experimental therapeutics2017
Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites.
Article in The Journal of pharmacology and experimental therapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 35 citations in OpenAlex.
- CYP1B1- and CYP1A1-Template systems and their application to metabolism and inhibition.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Role of Cytochromes P450 in Intestinal Barrier Function: Possible Involvement in the Pathogenesis of Leaky Gut Syndrome.Digestive diseases and sciences · 2025Review
- A New Algorithm Integrating Molecular Response, Toxicity, and Plasma Level Measures for Ponatinib Dose Choice in Patients Affected by Chronic Myeloid Leukemia.Pharmaceutics · 2024Article
- Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: a review.Molecular and cellular biochemistry · 2022Review
- Sex-related differential susceptibility to ponatinib cardiotoxicity and differential modulation of the Notch1 signalling pathway in a murine model.Journal of cellular and molecular medicine · 2022Article
- Advances in the study of drug metabolism - symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX).Drug metabolism reviews · 2020Review
- Utilizing Stimulated Raman Scattering Microscopy To Study Intracellular Distribution of Label-Free Ponatinib in Live Cells.Journal of medicinal chemistry · 2020Article
- Human Cytochrome P450 1A1 Adapts Active Site for Atypical Nonplanar Substrate.Drug metabolism and disposition: the biological fate of chemicals · 2020Article
- Defining the Contribution of CYP1A1 and CYP1A2 to Drug Metabolism Using Humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 Knockout Mice.Drug metabolism and disposition: the biological fate of chemicals · 2019Article
- Structures of human cytochrome P450 1A1 with bergamottin and erlotinib reveal active-site modifications for binding of diverse ligands.The Journal of biological chemistry · 2018Article
- P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic Metabolism and Toxicity.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Role of Cytochrome P450 Enzymes in the Metabolic Activation of Tyrosine Kinase Inhibitors.International journal of molecular sciences · 2018Review
- The role of hepatic cytochrome P450s in the cytotoxicity of dronedarone.Archives of toxicology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Ponatinib, a pan-BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML), causes severe side effects including vascular occlusions, pancreatitis, and liver toxicity, although the underlying mechanisms remain unclear. Modifications of critical proteins through reactive metabolites are thought to be responsible for a number of adverse drug reactions. In vitro metabolite screening of ponatinib with human liver microsomes and glutathione revealed unambiguous signals of ponatinib-glutathione (P-GSH) adducts. Further profiling of human cytochrome P450 (P450) indicated that CYP1A1 was the predominant P450 enzyme driving this reaction. P-GSH conjugate formation paralleled the disappearance of hydroxylated ponatinib metabolites, suggesting the initial reaction was epoxide generation. Mouse glutathione
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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.