ArticleThe Journal of pharmacology and experimental therapeutics2013
Substrate-dependent ligand inhibition of the human organic cation transporter OCT2.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Article
- Computational Approaches for Predicting Drug Interactions with Human Organic Anion Transporter 4 (OAT4).Molecular pharmaceutics · 2025Article
- In silico design and computational screening of berberine derivatives for potential antidiabetic activity through allosteric activation of the AMPK pathway.In silico pharmacology · 2025Article
- Identification of Natural Terpenoid Compounds as Potential Inhibitors of Nucleoprotein of Influenza A Virus usingMedicinal chemistry (Shariqah (United Arab Emirates)) · 2025Article
- Characterization of Human Organic Anion Transporter 4 (hOAT4) and Mouse Oat5 (mOat5) As Functional Orthologs for Renal Anion Uptake and Efflux Transport.The Journal of pharmacology and experimental therapeutics · 2024Article
- Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Characterization of ligand-induced thermal stability of the human organic cation transporter 2 (OCT2).Frontiers in pharmacology · 2023Article
- Investigations with Drugs and Pesticides Revealed New Species- and Substrate-Dependent Inhibition by Elacridar and Imazalil inInternational journal of molecular sciences · 2022Article
- Novel method for kinetic analysis applied to transport by the uniporter OCT2.American journal of physiology. Renal physiology · 2022Article
- Magnitude of Drug-Drug Interactions in Special Populations.Pharmaceutics · 2022Review
- Removal of lycopene substrate inhibition enables high carotenoid productivity in Yarrowia lipolytica.Nature communications · 2022Article
- Transport Turnover Rates for Human OCT2 and MATE1 Expressed in Chinese Hamster Ovary Cells.International journal of molecular sciences · 2022Article
- Multitargeting nature of muscarinic orthosteric agonists and antagonists.Frontiers in physiology · 2022Review
- Substrate-DependentInternational journal of molecular sciences · 2021Article
- Article
- Cationic Compounds with SARS-CoV-2 Antiviral Activity and Their Interaction with Organic Cation Transporter/Multidrug and Toxin Extruder Secretory Transporters.The Journal of pharmacology and experimental therapeutics · 2021Article
- In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs.International journal of molecular sciences · 2021Article
- Comparison of Hepatic Transporter Tissue Expression in Rodents and Interspecies Hepatic OCT1 Activity.The AAPS journal · 2021Article
- General Overview of Organic Cation Transporters in Brain.Handbook of experimental pharmacology · 2021Article
- Drug-Drug Interactions at Organic Cation Transporter 1.Frontiers in pharmacology · 2021Review
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5 authors.
Funding
Abstract
Organic cation transporter 2 (OCT2) mediates the initial step in renal secretion of organic cations: uptake from the blood, across the basolateral membrane, and into the renal proximal tubule cells. Because of its potential as a target for unwanted drug-drug interactions (DDIs), considerable attention has been directed toward understanding the basis of OCT2 selectivity. These studies typically assess selectivity based on ligand inhibition profiles for OCT2-mediated transport of a probe substrate. However, little attention has been given to the potential influence of the substrate on the profile of ligand inhibition. Here we compared the IC50 values obtained for a set of structurally distinct inhibitors against OCT2-mediated transport of three structurally distinct substrates: 1-methyl-4-phenylpyridinium (MPP); metformin; and a novel fluorescent substrate, N,N,N-trimethyl-2-[methyl(7-nitrobenzo[c][l,2,5]oxadiazol-4-yl)amino]ethanaminium iodide (NBD-MTMA). The median IC50 value for inhibition of MPP transport was 9-fold higher than that for inhibition of metformin transport. Similarly, the median IC50 value for inhibition of MPP transport was 5-fold higher than that for NBD-MTMA transport. However, this was not a systematic difference in inhibitory efficacy; the ratio of IC50 values, MPP versus NBD-MTMA, ranged from 88-fold (ipratropium) to 0.3-fold (metformin). These data show that 1) the choice of OCT2 substrate significantly influences both quantitative and qualitative inhibitory interactions with cationic drugs; and 2) ligand interactions with OCT2 are not restricted to competition for a common ligand binding site, consistent with a binding surface characterized by multiple, possibly overlapping interaction sites. Development of predictive models of DDIs with OCT2 must take into account the substrate dependence of ligand interaction with this protein.
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