ArticlePharmaceutical research2015
Brain and Testis Accumulation of Regorafenib is Restricted by Breast Cancer Resistance Protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1).
Article in Pharmaceutical research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 69 citations in OpenAlex.
- Obesity Triggers Dysregulation of Essential ABC Transporters in Rat Testis and Sperm.Nutrients · 2026Article
- Development of a UPLC-MS/MS method and its application for the pharmacokinetic analysis of regorafenib in rats.Scientific reports · 2026Article
- Insights and perspectives into the etiology of TKI-induced cardiotoxicity.ASPET discovery · 2026Article
- Early Higher Plasma Regorafenib Concentration Predicts Shorter PFS in Japanese Patients With mCRC.Clinical and translational science · 2025Article
- Repurposing the Tyrosine Kinase Inhibitors Targeting FGFR and VEGFR Pathways for Cancer Therapy: A Comprehensive Review.Cancers · 2025Review
- Predictors of chemotherapy-related unplanned acute care in outpatients receiving oral anticancer drugs.Scientific reports · 2025Article
- Liraglutide and denatonium benzoate attenuate T2DM-induced metabolic, neurological, and testicular changes in rats: Targeting oxidative stress, inflammation, and BCRP transporter.Journal of molecular histology · 2025Article
- Article
- Breast cancer: miRNAs monitoring chemoresistance and systemic therapy.Frontiers in oncology · 2023Review
- Tyrosine Kinase Inhibitors for Glioblastoma Multiforme: Challenges and Opportunities for Drug Delivery.Pharmaceutics · 2022Review
- Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers.Cancers · 2022Review
- Ferroptosis and Tumor Drug Resistance: Current Status and Major Challenges.Frontiers in pharmacology · 2022Review
- Breast cancer: molecular mechanisms of underlying resistance and therapeutic approaches.American journal of cancer research · 2022Review
- Review
- Pharmacokinetics of the oral multikinase inhibitor regorafenib and its association with real-world treatment outcomes.Investigational new drugs · 2021Article
- Novel Receptor Tyrosine Kinase Pathway Inhibitors for Targeted Radionuclide Therapy of Glioblastoma.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Associations among plasma concentrations of regorafenib and its metabolites, adverse events, and ABCG2 polymorphisms in patients with metastatic colorectal cancers.Cancer chemotherapy and pharmacology · 2021Observational
- Extrahepatic metabolism of ibrutinib.Investigational new drugs · 2021Article
- Low-intermediate dose of lenvatinib in anaplastic thyroid cancer is highly effective and safe.BMJ case reports · 2020Article
- Generation of a hTERT-Immortalized Human Sertoli Cell Model to Study Transporter Dynamics at the Blood-Testis Barrier.Pharmaceutics · 2020Article
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
purposeRegorafenib is a novel multikinase inhibitor, currently approved for the treatment of metastasized colorectal cancer and advanced gastrointestinal stromal tumors. We investigated whether regorafenib is a substrate for the multidrug efflux transporters ABCG2 and ABCB1 and whether oral availability, brain and testis accumulation of regorafenib and its active metabolites are influenced by these transporters.
methodsWe used in vitro transport assays to assess human (h)ABCB1- or hABCG2- or murine (m)Abcg2-mediated active transport at high and low concentrations of regorafenib. To study the single and combined roles of Abcg2 and Abcb1a/1b in oral regorafenib disposition and the impact of Cyp3a-mediated metabolism, we used appropriate knockout mouse strains.
resultsRegorafenib was transported well by mAbcg2 and hABCG2 and modestly by hABCB1 in vitro. Abcg2 and to a lesser extent Abcb1a/1b limited brain and testis accumulation of regorafenib and metabolite M2 (brain only) in mice. Regorafenib oral availability was not increased in Abcg2(-/-);Abcb1a/1b(-/-) mice. Up till 2 h, metabolite M5 was undetectable in plasma and organs.
conclusionsBrain and testis accumulation of regorafenib and brain accumulation of metabolite M2 are restricted by Abcg2 and Abcb1a/1b. Inhibition of these transporters may be of clinical relevance for patients with brain (micro)metastases positioned behind an intact blood-brain barrier.
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