ArticlePharmaceutical research2012
In vitro and in silico strategies to identify OATP1B1 inhibitors and predict clinical drug-drug interactions.
Article in Pharmaceutical research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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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
38 citing papers in PubMed, 119 citations in OpenAlex.
- Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline.Journal of clinical pharmacology · 2015Trial
- Trial
- Prevalence of substances with OATP1B1 inhibitory properties in individual case safety reports of suspected statin-associated myopathy - an analysis of Swiss pharmacovigilance data.European journal of clinical pharmacology · 2026Article
- Probe substrates assay estimates the effect of polyphyllin H on the activity of cytochrome P450 enzymes in human liver microsomes.Pharmacology research & perspectives · 2024Article
- Pharmaceutical Quality by Design Approach to Develop High-Performance Nanoparticles for Magnetic Hyperthermia.ACS nano · 2024Article
- Screening oral drugs for their interactions with the intestinal transportome via porcine tissue explants and machine learning.Nature biomedical engineering · 2024Article
- Systems biology approaches to identify driver genes and drug combinations for treating COVID-19.Scientific reports · 2024Article
- Establishment of UGT1A1-knockout human iPS-derived hepatic organoids for UGT1A1-specific kinetics and toxicity evaluation.Molecular therapy. Methods & clinical development · 2023Article
- Mechanistic in vitro studies indicate that the clinical drug-drug interactions between protease inhibitors and rosuvastatin are driven by inhibition of intestinal BCRP and hepatic OATP1B1 with minimal contribution from OATP1B3, NTCP and OAT3.Pharmacology research & perspectives · 2023Article
- Machine Learning Models Identify New Inhibitors for Human OATP1B1.Molecular pharmaceutics · 2022Article
- Physiological Characterization of the Transporter-Mediated Uptake of the Reversible Male Contraceptive H2-Gamendazole Across the Blood-Testis Barrier.The Journal of pharmacology and experimental therapeutics · 2022Article
- Molecular Properties of Drugs Handled by Kidney OATs and Liver OATPs Revealed by Chemoinformatics and Machine Learning: Implications for Kidney and Liver Disease.Pharmaceutics · 2021Article
- Is It Time to Use Modeling of Cellular Transporter Homeostasis to Inform Drug-Drug Interaction Studies: Theoretical Considerations.The AAPS journal · 2021Article
- Data-Driven Ensemble Docking to Map Molecular Interactions of Steroid Analogs with Hepatic Organic Anion Transporting Polypeptides.Journal of chemical information and modeling · 2021Article
- Mouse NTCP-Mediated Rosuvastatin Uptake In Vitro and in Slc10a1-Deficient Mice.The AAPS journal · 2021Article
- Mechanistic Computational Models of Epithelial Cell Transporters-the Adorned Heroes of Pharmacokinetics.Frontiers in pharmacology · 2021Review
- Article
- An Informatics-based Approach to Identify Key Pharmacological Components in Drug-Drug Interactions.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2020Article
- Current Advances in Studying Clinically Relevant Transporters of the Solute Carrier (SLC) Family by Connecting Computational Modeling and Data Science.Computational and structural biotechnology journal · 2019Review
- Repaglinide-irbesartan drug interaction: effects of SLCO1B1 polymorphism on repaglinide pharmacokinetics and pharmacodynamics in Chinese population.European journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo establish in vitro and in silico models that predict clinical drug-drug interactions (DDIs) with the OATP1B1 (SLCO1B1) transporter.
methodsThe inhibitory effect of 146 drugs and drug-like compounds on OATP1B1-mediated transport was studied in HEK293 cells. A computational model was developed to predict OATP1B1 inhibition. Concentration-dependent effects were investigated for six compounds; clinical DDIs were predicted by calculating change in exposure (i.e. R-values) in eight different ways.
resultsSixty-five compounds were identified as OATP1B1 inhibitors at 20 μM. The computational model predicted the test set with 80% accuracy for inhibitors and 91% for non-inhibitors. In vitro-in vivo comparisons underscored the importance of using drugs with known clinical effects as references. Thus, reference drugs, cyclosporin A, gemfibrozil, and fenofibrate, provided an inhibition interval to which three antiviral drugs, atazanavir, lopinavir, and amprenavir, could be compared and their clinical DDIs with OATP1B1 classified.
conclusionsTwenty-two new OATP1B1 inhibitors were identified, a predictive OATP1B1 inhibition in silico model was developed, and successful predictions of clinical DDIs were obtained with OATP1B1.
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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.