ArticlePharmaceutical research2009
Novel inhibitors of human organic cation/carnitine transporter (hOCTN2) via computational modeling and in vitro testing.
Article in Pharmaceutical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 39 citations in OpenAlex.
- Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs.Pharmaceutics · 2023Review
- 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
- Comparison of Deep Learning With Multiple Machine Learning Methods and Metrics Using Diverse Drug Discovery Data Sets.Molecular pharmaceutics · 2017Article
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Making Transporter Models for Drug-Drug Interaction Prediction Mobile.Drug metabolism and disposition: the biological fate of chemicals · 2015Article
- Quantitative NTCP pharmacophore and lack of association between DILI and NTCP Inhibition.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2015Article
- Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction.The Journal of biological chemistry · 2014Article
- Uptake carriers and oncology drug safety.Drug metabolism and disposition: the biological fate of chemicals · 2014Review
- A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus.F1000Research · 2014Article
- Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP).Molecular pharmaceutics · 2013Article
- Computational modeling to accelerate the identification of substrates and inhibitors for transporters that affect drug disposition.Clinical pharmacology and therapeutics · 2012Article
- Molecular determinants of ligand selectivity for the human multidrug and toxin extruder proteins MATE1 and MATE2-K.The Journal of pharmacology and experimental therapeutics · 2012Article
- A substrate pharmacophore for the human organic cation/carnitine transporter identifies compounds associated with rhabdomyolysis.Molecular pharmaceutics · 2012Article
- Inhibition of OCTN2-mediated transport of carnitine by etoposide.Molecular cancer therapeutics · 2012Article
- Finding promiscuous old drugs for new uses.Pharmaceutical research · 2011Article
- The evolution of farnesoid X, vitamin D, and pregnane X receptors: insights from the green-spotted pufferfish (Tetraodon nigriviridis) and other non-mammalian species.BMC biochemistry · 2011Article
- Quantitative structure activity relationship for inhibition of human organic cation/carnitine transporter.Molecular pharmaceutics · 2010Article
- Reliability of inhibition models to correctly identify type of inhibition.Pharmaceutical research · 2010Article
- Cisplatin-induced downregulation of OCTN2 affects carnitine wasting.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Article
- Why we should be vigilant: drug cytotoxicity observed with in vitro transporter inhibition studies.Biochemical pharmacology · 2010Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe objective was to elucidate the inhibition requirements of the human organic cation/carnitine transporter (hOCTN2).
methodsTwenty-seven drugs were screened initially for their potential to inhibit uptake of L-carnitine into a stably transfected hOCTN2-MDCK cell monolayer. A HipHop common features pharmacophore was developed and used to search a drug database. Fifty-three drugs, including some not predicted to be inhibitors, were selected and screened in vitro.
resultsA common features pharmacophore was derived from initial screening data and consisted of three hydrophobic features and a positive ionizable feature. Among the 33 tested drugs that were predicted to map to the pharmacophore, 27 inhibited hOCTN2 in vitro (40% or less L-carnitine uptake from 2.5 microM L-carnitine solution in presence of 500 microM drug, compared to L-carnitine uptake without drug present). Hence, the pharmacophore accurately prioritized compounds for testing. K(i) measurements showed low micromolar inhibitors belonged to diverse therapeutic classes of drugs, including many not previously known to inhibit hOCTN2. Compounds were more likely to cause rhabdomyolysis if the C(max)/K(i) ratio was higher than 0.0025.
conclusionA combined pharmacophore and in vitro approach found new, structurally diverse inhibitors for hOCTN2 that may possibly cause clinical significant toxicity such as rhabdomyolysis.
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