ArticlePharmaceutical research2015
Breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (P-GP/ABCB1) restrict oral availability and brain accumulation of the PARP inhibitor rucaparib (AG-014699).
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 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- Decoding PARP roles in breast cancer therapy resistance.Molecular biology reports · 2026Review
- Development and Validation of an SPE-LC-MS Method for the Determination of Epirubicin, Olaparib and Ribociclib in Human Serum.Biomedicines · 2026Article
- Clinical application of PARP inhibitors and emerging strategies to overcome resistance: a pan-cancer perspective.Biomarker research · 2026Review
- (N)-Methanocarba Adenosine Derivatives as Dual Modulators of P-Glycoprotein and ABCG2 Transporters.Journal of medicinal chemistry · 2026Article
- Glioblastoma and PARP inhibitors: the importance of patient selection to maximize therapeutic benefits. A critical review.Frontiers in oncology · 2026Review
- Peptide-based strategies for overcoming taxol-resistance in cancer therapy - a narrative review.Pharmacological reports : PR · 2025Review
- Mechanisms of Resistance to PARPi in Pancreatic Ductal Adenocarcinoma.Journal of cellular and molecular medicine · 2025Article
- The "specific" P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Case Report: Abiraterone in brain metastases from prostate cancer.Frontiers in oncology · 2025Article
- Review
- Synthetically accessible de novo design using reaction vectors: Application to PARP1 inhibitors.Molecular informatics · 2024Article
- Small molecule agents for triple negative breast cancer: Current status and future prospects.Translational oncology · 2024Review
- Dramatic, durable response to therapy in gBRCA2-mutated pancreas neuroendocrine carcinoma: opportunity and challenge.NPJ precision oncology · 2023Article
- Transporter‑mediated drug‑drug interactions involving poly (ADP‑ribose) polymerase inhibitors (Review).Oncology letters · 2023Review
- [1,2,4]Triazolo[3,4-Journal of medicinal chemistry · 2023Article
- Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer.Frontiers in pharmacology · 2023Review
- OGG1 competitive inhibitors show important off-target effects by directly inhibiting efflux pumps and disturbing mitotic progression.Frontiers in cell and developmental biology · 2023Article
- Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in non-alcoholic steatohepatitis patients.Acta pharmaceutica Sinica. B · 2023Review
- Pharmacokinetics and Pharmacodynamics of PARP Inhibitors in Oncology.Clinical pharmacokinetics · 2022Review
- Design and synthesis of benzodiazepines as brain penetrating PARP-1 inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
4 more citing papers are in PubMed but not listed here.
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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
backgroundRucaparib is a potent, orally available, small-molecule inhibitor of poly ADP-ribose polymerase (PARP) 1 and 2. Ongoing clinical trials are assessing the efficacy of rucaparib alone or in combination with other cytotoxic drugs, mainly in breast and ovarian cancer patients with mutations in the breast cancer associated (BRCA) genes. PURPOSE: We aimed to establish whether the multidrug efflux transporters ABCG2 (BCRP) and ABCB1 (P-gp, MDR1) affect the oral availability and brain penetration of rucaparib in mice.
resultsIn vitro, rucaparib was efficiently transported by both human ABCB1 and ABCG2, and very efficiently by mouse Abcg2. Transport could be inhibited by the small-molecule ABCB1 and ABCG2 inhibitors zosuquidar and Ko143, respectively. In vivo, oral availability (plasma AUC0-1 and AUC0-24) and brain levels of rucaparib at 1 and 24 h were increased by the absence of both Abcg2 and Abcb1a/1b after oral administration of rucaparib at 10 mg/kg.
conclusionsOur data show to our knowledge for the first time that oral availability and brain accumulation of a PARP inhibitor are markedly and additively restricted by Abcg2 and Abcb1a/1b. This may have clinical relevance for improvement of rucaparib therapy in PARP inhibitor-resistant tumors with ABCB1 and/or ABCG2 expression and in patients with brain (micro)metastases positioned behind a functional blood-brain barrier.
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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.