ArticleCancer chemotherapy and pharmacology2009
Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4'-methanol-bisbenzonitrile in vitro.
Article in Cancer chemotherapy and pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Systematic Review of Naturally Derived Substances That Act as Inhibitors of the Nicotine Metabolizing Enzyme Cytochrome P450 2A6.International journal of molecular sciences · 2024Pooled it
- Plasma letrozole concentrations in postmenopausal women with breast cancer are associated with CYP2A6 genetic variants, body mass index, and age.Clinical pharmacology and therapeutics · 2011Trial
- Aromatase Inhibitor Therapy Is Associated with Distinct Plasma Lipidomic Profiles in Postmenopausal Breast Cancer Patients.International journal of molecular sciences · 2026Article
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- A Rare Presentation of Metastatic Breast Cancer Manifesting As Diffuse Nodular Skin Lesions.Cureus · 2023Article
- Pyridine based dual binding site aromatase (CYP19A1) inhibitors.RSC medicinal chemistry · 2023Article
- Enriching Medication Review with a Pharmacogenetic Profile - A Case of Tamoxifen Adverse Drug Reactions.Pharmacogenomics and personalized medicine · 2021Article
- Genetic Underpinnings of Musculoskeletal Pain During Treatment With Aromatase Inhibitors for Breast Cancer: A Biological Pathway Analysis.Biological research for nursing · 2020Article
- Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis.Molecules (Basel, Switzerland) · 2020Article
- Characterization of Maternal and Fetal CYP3A-Mediated Progesterone Metabolism.Fetal and pediatric pathology · 2017Article
- Comprehensive and Automated Linear Interaction Energy Based Binding-Affinity Prediction for Multifarious Cytochrome P450 Aromatase Inhibitors.Journal of chemical information and modeling · 2017Article
- CYP1A2--a novel genetic marker for early aromatase inhibitor response in the treatment of breast cancer patients.BMC cancer · 2016Article
- Determining the IC 50 Values for Vorozole and Letrozole, on a Series of Human Liver Cytochrome P450s, to Help Determine the Binding Site of Vorozole in the Liver.Enzyme research · 2015Article
- Inhibition of cytochrome p450 enzymes by the e- and z-isomers of norendoxifen.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Novel aromatase inhibitors by structure-guided design.Journal of medicinal chemistry · 2012Article
- PharmGKB summary: very important pharmacogene information for cytochrome P-450, family 2, subfamily A, polypeptide 6.Pharmacogenetics and genomics · 2012Review
- Efavirenz primary and secondary metabolism in vitro and in vivo: identification of novel metabolic pathways and cytochrome P450 2A6 as the principal catalyst of efavirenz 7-hydroxylation.Drug metabolism and disposition: the biological fate of chemicals · 2010Article
- The use of aromatase inhibitors in boys with short stature: what to know before prescribing?Archives of endocrinology and metabolismReview
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo determine the inhibitory potency of letrozole and its main human metabolite, 4,4'-methanol-bisbenzonitrile, on the activities of eight cytochrome P450 (CYP) enzymes.
methodsLetrozole and its metabolite were incubated with human liver microsomes (HLMs) (or expressed CYP isoforms) and NADPH in the absence (control) and presence of the test inhibitor.
resultsLetrozole was a potent competitive inhibitor of CYP2A6 (K (i) 4.6 +/- 0.05 microM and 5.0 +/- 2.4 microM in HLMs and CYP2A6, respectively) and a weak inhibitor of CYP2C19 (K (i) 42.2 microM in HLMs and 33.3 microM in CYP2C19), while its metabolite showed moderate inhibition of CYP2C19 and CYP2B6. Letrozole or its metabolite had negligible effect on other CYPs.
conclusionsBased on the in vitro K (i) values, letrozole is predicted to be a weak inhibitor of CYP2A6 in vivo. Letrozole and its major human metabolite show inhibitory activity towards other CYPs, but clinically relevant drug interactions seem less likely as the K (i) values are above the therapeutic plasma concentrations of letrozole.
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