ArticleNature structural & molecular biology2023
Molecular basis of polyspecific drug and xenobiotic recognition by OCT1 and OCT2.
Article in Nature structural & molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Population pharmacokinetic modeling of amisulpride drug interactions and a transporter binding analysis.European journal of clinical pharmacology · 2026Article
- Structural and biochemical comparison of the FLVCR and CTL membrane protein families in eukaryotes.Life science alliance · 2026Article
- L-Type Voltage-Gated CaMedical sciences (Basel, Switzerland) · 2026Article
- Identification of Brimonidine as a Novel Substrate of Organic Cation Transporters OCT2 and MATE1 Expressed in Human Eye.Investigative ophthalmology & visual science · 2026Article
- The 2-Amino-3,4-dihydroquinazoline Molecular Scaffold as Novel OCT3 Inhibitor.ACS chemical neuroscience · 2026Article
- Intracellular Pharmacokinetics of Antidiabetic Drugs: A Focused Narrative Review of Subcellular Distribution (2015-2025).Diseases (Basel, Switzerland) · 2026Review
- Applying molecular dynamics simulations to validate OCT1 substrates uncovers vitamin K1 as a high-affinity ligand.Frontiers in pharmacology · 2026Article
- Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular basis of prostaglandin ENature communications · 2025Article
- Structural basis of sodium ion-dependent carnitine transport by OCTN2.Nature communications · 2025Article
- Transport of Small Aliphatic Amines by Polyspecific Solute Carriers: Deciphering Structure-Function Relationships.ACS pharmacology & translational science · 2025Article
- Metformin and Adipose Tissue: A Multifaceted Regulator in Metabolism, Inflammation, and Regeneration.Endocrinology and metabolism (Seoul, Korea) · 2025Review
- Substrate Specificity of the Organic Cation Transporters MATE1 and MATE2K and Functional Overlap with OCT1 and OCT2.Journal of medicinal chemistry · 2025Article
- Molecular basis of the urate transporter URAT1 inhibition by gout drugs.Nature communications · 2025Article
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Verapamil and its metabolite norverapamil inhibit theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens.Cell chemical biology · 2025Review
- Article
- Structures and membrane interactions of human OAT1 in complex with clinical used drugs.Science advances · 2025Article
- Cryo-EM structure of the botulinum neurotoxin A/SV2B complex and its implications for translocation.Nature communications · 2025Article
Corrections and comments
- Update of
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
A wide range of endogenous and xenobiotic organic ions require facilitated transport systems to cross the plasma membrane for their disposition. In mammals, organic cation transporter (OCT) subtypes 1 and 2 (OCT1 and OCT2, also known as SLC22A1 and SLC22A2, respectively) are polyspecific transporters responsible for the uptake and clearance of structurally diverse cationic compounds in the liver and kidneys, respectively. Notably, it is well established that human OCT1 and OCT2 play central roles in the pharmacokinetics and drug-drug interactions of many prescription medications, including metformin. Despite their importance, the basis of polyspecific cationic drug recognition and the alternating access mechanism for OCTs have remained a mystery. Here we present four cryo-electron microscopy structures of apo, substrate-bound and drug-bound OCT1 and OCT2 consensus variants, in outward-facing and outward-occluded states. Together with functional experiments, in silico docking and molecular dynamics simulations, these structures uncover general principles of organic cation recognition by OCTs and provide insights into extracellular gate occlusion. Our findings set the stage for a comprehensive structure-based understanding of OCT-mediated drug-drug interactions, which will prove critical in the preclinical evaluation of emerging therapeutics.
Indexed as
Identifiers
What OpenQuestion holds
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.