{"doi":"10.1007/s11095-011-0429-2","title":"The Role of Constitutive Androstane Receptor in Oxazaphosphorine-Mediated Induction of Drug-Metabolizing Enzymes in Human Hepatocytes","abstract":null,"journal":"Pharmaceutical Research","year":2011,"id":635022,"datarank":0.47670807455219194,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.0,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":816976,"name":"Linhao Li","orcid":"0000-0002-3207-9740","position":1,"is_corresponding":false},{"id":1647266,"name":"Jennifer Fuhrman","orcid":null,"position":2,"is_corresponding":false},{"id":297211,"name":"Stephen Ferguson","orcid":"0000-0003-3172-8347","position":3,"is_corresponding":false},{"id":399905,"name":"Hongbing Wang","orcid":"0000-0002-7362-7854","position":4,"is_corresponding":false},{"id":1442521,"name":"Duan Wang","orcid":"0000-0001-5487-4414","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The Role of Constitutive Androstane Receptor in Oxazaphosphorine-Mediated Induction of Drug-Metabolizing Enzymes in Human Hepatocytes","abstract":"<h4>Purpose</h4>To investigate the roles of the constitutive androstane receptor (CAR) in cyclophosphamide (CPA)- and ifosfamide (IFO)-mediated induction of hepatic drug-metabolizing enzymes (DME).<h4>Methods</h4>Induction of DMEs was evaluated using real-time RT-PCR and Western blotting analysis in human primary hepatocyte (HPH) cultures. Activation of CAR, pregnane X receptor (PXR), and aryl hydrocarbon receptor by CPA and IFO was assessed in cell-based reporter assays in HepG2 cells and/or nuclear translocation assays in HPHs.<h4>Results</h4>CYP2B6 reporter activity was significantly enhanced by CPA and IFO in HepG2 cells co-transfected with CYP2B6 reporter plasmid and a chemical-responsive human CAR variant (CAR1 + A) construct. Real-time RT-PCR and Western blotting analysis in HPHs showed that both CPA and IFO induced the expressions of CYP2B6 and CYP3A4. Notably, treatment of HPHs with CPA but not IFO resulted in significant nuclear accumulation of CAR, which represents the initial step of CAR activation. Further studies in HPHs demonstrated that selective inhibition of PXR by sulforaphane preferentially repressed IFO- over CPA-mediated induction of CYP2B6.<h4>Conclusion</h4>These results provide novel insights into the differential roles of CAR in the regulation of CPA- and IFO-induced DME expression and potential drug-drug interactions.","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21487929","pmcid":"PMC3703447","openalex_id":"https://openalex.org/W1973422270","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK061652","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01DK061652-12","title":"Regulation of CYP2B6 in Human Liver"}],"total_grants":2,"fwci":2.8718,"citation_percentile":0.89281748,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":3},{"year":2014,"count":1},{"year":2015,"count":4},{"year":2016,"count":3},{"year":2017,"count":1},{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":4},{"year":2023,"count":1}],"oa_status":"closed","license":"Springer TDM","oa_locations":[{"url":"http://link.springer.com/content/pdf/10.1007/s11095-011-0429-2.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1007/s11095-011-0429-2/fulltext.html","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1007/s11095-011-0429-2","host_type":"publisher"},{"url":"https://doi.org/10.1007/s11095-011-0429-2","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21487929","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3703447","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc3703447?pdf=render","host_type":""},{"url":"https://dx.doi.org/10.1007/s11095-011-0429-2","host_type":""}],"fields_of_study":["Pharmacogenetics and Drug Metabolism","Chemotherapy-induced organ toxicity mitigation","Drug-Induced Hepatotoxicity and Protection","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Pregnane X Receptor","Constitutive Androstane Receptor","Aryl Hydrocarbon Hydroxylases","Cells, Cultured","Cyclophosphamide","Drug Interactions","Enzyme Induction","Humans","Ifosfamide","Liver","Inactivation, Metabolic","Oxidoreductases, N-Demethylating","Receptors, Steroid","Receptors, Cytoplasmic and Nuclear","Receptors, Aryl Hydrocarbon","Hepatocytes","Cytochrome P-450 CYP3A","Hep G2 Cells","Cytochrome P-450 CYP2B6"],"keywords":["Constitutive androstane receptor","Drug","Enzyme","Pharmacology","Enzyme inducer","Receptor","Cytochrome P450","Androstane","Chemistry","Biology","Biochemistry","Nuclear receptor","Endocrinology","Transcription factor","Gene","Receptors, Steroid","Pregnane X Receptor","Receptors, Cytoplasmic and Nuclear","Oxidoreductases, N-Demethylating","Hep G2 Cells","Cytochrome P-450 CYP2B6","Liver","Receptors, Aryl Hydrocarbon","Enzyme Induction","Inactivation, Metabolic","Hepatocytes","Cytochrome P-450 CYP3A","Humans","Drug Interactions","Aryl Hydrocarbon Hydroxylases","Ifosfamide","Cyclophosphamide","Cells, Cultured"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T14:32:22.728914Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}