ArticleDrug metabolism and disposition: the biological fate of chemicals2016
Tariquidar Is an Inhibitor and Not a Substrate of Human and Mouse P-glycoprotein.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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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.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- An Approach Toward Radioiodination and Radiopharmacological Evaluation of a Carborane-Containing Analog of Indomethacin.Molecules (Basel, Switzerland) · 2026Article
- In Silico Prediction and Validation of the Permeability of Small Molecules Across the Blood-Brain Barrier.International journal of molecular sciences · 2026Article
- Simulation and Machine Learning Assessment of P-Glycoprotein Pharmacology in the Blood-Brain Barrier: Inhibition and Substrate Transport.International journal of molecular sciences · 2025Article
- Anticancer activity of triterpene glycosides from the sea star Solaster pacificus.Scientific reports · 2025Article
- Review
- Pharmacokinetic Modeling of the Effect of Tariquidar on Ondansetron Disposition into the Central Nervous System.Pharmaceutical research · 2024Article
- Development of an orally bioavailable mSWI/SNF ATPase degrader and acquired mechanisms of resistance in prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Zosuquidar: An Effective Molecule for Intracellular CaInternational journal of molecular sciences · 2024Article
- Modeling Substrate Entry into the P-Glycoprotein Efflux Pump at the Blood-Brain Barrier.Journal of medicinal chemistry · 2023Article
- A Novel 3-ACS omega · 2023Article
- Metabolic Engineering ofJournal of fungi (Basel, Switzerland) · 2023Article
- Essential role of P-glycoprotein in the mechanism of action of oliceridine.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- The Molecular Mechanisms of Oleanane Aldehyde-β-enone Cytotoxicity against Doxorubicin-Resistant Cancer Cells.Biology · 2023Article
- Cytotoxic N-Methylpretrichodermamide B Reveals Anticancer Activity and Inhibits P-Glycoprotein in Drug-Resistant Prostate Cancer Cells.Marine drugs · 2022Article
- The drug efflux pump MDR1 promotes intrinsic and acquired resistance to PROTACs in cancer cells.Science signaling · 2022Article
- New diterpenes from the marine sponge Spongionella sp. overcome drug resistance in prostate cancer by inhibition of P-glycoprotein.Scientific reports · 2022Article
- Acquired Drug Resistance Enhances Imidazoquinoline Efflux by P-Glycoprotein.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Drug and Solute Transporters in Mediating Resistance to Novel Therapeutics in Multiple Myeloma.ACS pharmacology & translational science · 2021Review
- Inhibition of P-Glycoprotein Does Not Increase the Efficacy of Proteasome Inhibitors in Multiple Myeloma Cells.ACS pharmacology & translational science · 2021Article
- P-Glycoprotein Inhibitor Tariquidar Plays an Important Regulatory Role in Pigmentation in Larval Zebrafish.Cells · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Since its development, tariquidar (TQR; XR9576; N-[2-[[4-[2-(6,7-Dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethyl]phenyl]carbamoyl]-4,5-dimethoxyphenyl]quinoline-3-carboxamide) has been widely regarded as one of the more potent inhibitors of P-glycoprotein (P-gp), an efflux transporter of the ATP-binding cassette (ABC) transporter family. A third-generation inhibitor, TQR exhibits high affinity for P-gp, although it is also a substrate of another ABC transporter, breast cancer resistance protein (BCRP). Recently, several studies have questioned the mechanism by which TQR interfaces with P-gp, suggesting that TQR is a substrate for P-gp instead of a noncompetitive inhibitor. We investigated TQR and its interaction with human and mouse P-gp to determine if TQR is a substrate of P-gp in vitro. To address these questions, we used multiple in vitro transporter assays, including cytotoxicity, flow cytometry, accumulation, ATPase, and transwell assays. A newly generated BCRP cell line was used as a positive control that demonstrates TQR-mediated transport. Based on our results, we conclude that TQR is a potent inhibitor of both human and mouse P-gp and shows no signs of being a substrate at the concentrations tested. These in vitro data further support our position that the in vivo uptake of [(11)C]TQR into the brain can be explained by its high-affinity binding to P-gp and by it being a substrate of BCRP, followed by amplification of the brain signal by ionic trapping in acidic lysosomes.
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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.