Full Text Journal Articles by
Author Stephen H Wright

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Cationic Compounds with SARS-CoV-2 Antiviral Activity and their Interaction with OCT/MATE Secretory Transporters.

Lucy Jazmin Martinez Guerrero, Xiaohong Zhang, Kimberley M Zorn, Sean Ekins, Stephen H Wright,

In the wake of the COVID-19 pandemic, drug repurposing has been highlighted for rapid introduction of therapeutics. Proposed drugs with activity against SARS-CoV-2 include compounds with positive charges at physiological pH, making them potential targets for the organic cation (OC) secretory transporters of kidney and liver, i.e., the basolateral Organic ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2021, :]

Cited: 0 times

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Multiple Computational Approaches for Predicting Drug Interactions with Human Equilibrative Nucleoside Transporter 1.

Siennah R Miller, Thomas R Lane, Kimberley M Zorn, Sean Ekins, Stephen H Wright, Nathan J Cherrington,

Equilibrativenucleoside transporters (ENTs) participate in the pharmacokinetics and disposition of nucleoside analog drugs. Understanding drug interactions with the ENTs may inform and facilitate the development of new drugs, including chemotherapeutics and antivirals that require access to sanctuary sites such as the male genital tract. This study created three-dimensional pharmacophores for ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2021, 49(7):479-489]

Cited: 1 time

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Predicting Drug Interactions with Human Equilibrative Nucleoside Transporters 1 and 2 Using Functional Knockout Cell Lines and Bayesian Modeling.

Siennah R Miller, Xiaohong Zhang, Raymond K Hau, Joseph L Jilek, Erin Q Jennings, James J Galligan, Daniel H Foil, Kimberley M Zorn, Sean Ekins, Stephen H Wright, Nathan J Cherrington,

Equilibrative nucleoside transporters (ENTs) 1 and 2 facilitate nucleoside transport across the blood-testis barrier (BTB). Improving drug entry into the testes with drugs that use endogenous transport pathways may lead to more effective treatments for diseases within the reproductive tract. In this study, CRISPR/CRISPR-associated protein 9 was used to generate ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2021, 99(2):147-162]

Cited: 2 times

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Generation of a hTERT-Immortalized Human Sertoli Cell Model to Study Transporter Dynamics at the Blood-Testis Barrier.

Raymond K Hau, Siennah R Miller, Stephen H Wright, Nathan J Cherrington,

The blood-testis barrier (BTB) formed by adjacent Sertoli cells (SCs) limits the entry of many chemicals into seminiferous tubules. Differences in rodent and human substrate-transporter selectivity or kinetics can misrepresent conclusions drawn using rodent in vitro models. Therefore, human in vitro models are preferable when studying transporter dynamics at the ... Read more >>

Pharmaceutics (Pharmaceutics)
[2020, 12(11):]

Cited: 1 time

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Molecular and cellular physiology of organic cation transporter 2.

Stephen H Wright,

Organic cation transporters play a critical role in mediating the distribution of cationic pharmaceuticals. Indeed, organic cation transporter (OCT)2 is the initial step in the renal secretion of organic cations and consequently plays a defining role in establishing the pharmacokinetics of many cationic drugs. Although a hallmark of OCTs is ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2019, 317(6):F1669-F1679]

Cited: 2 times

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Kinetic basis of metformin-MPP interactions with organic cation transporter OCT2.

Philip J Sandoval, Mark Morales, Timothy W Secomb, Stephen H Wright,

Organic cation transporter 2 (OCT2) clears the blood of cationic drugs. Efforts to understand OCT2 selectivity as a means to predict the potential of new molecular entities (NMEs) to produce unwanted drug-drug interactions typically assess the influence of the NMEs on inhibition of transport. However, the identity of the substrate ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2019, 317(3):F720-F734]

Cited: 2 times

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Assessment of Substrate-Dependent Ligand Interactions at the Organic Cation Transporter OCT2 Using Six Model Substrates.

Philip J Sandoval, Kimberley M Zorn, Alex M Clark, Sean Ekins, Stephen H Wright,

Organic cation transporter (OCT) 2 mediates the entry step for organic cation secretion by renal proximal tubule cells and is a site of unwanted drug-drug interactions (DDIs). But reliance on decision tree-based predictions of DDIs at OCT2 that depend on IC<sub>50</sub> values can be suspect because they can be influenced ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2018, 94(3):1057-1068]

Cited: 23 times

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Correlation between Apparent Substrate Affinity and OCT2 Transport Turnover.

Alyscia Cory Severance, Philip J Sandoval, Stephen H Wright,

Organic cation (OC) transporter 2 (OCT2) mediates the first step in the renal secretion of many cationic drugs: basolateral uptake from blood into proximal tubule cells. The impact of this process on the pharmacokinetics of drug clearance as estimated using a physiologically-based pharmacokinetic approach relies on an accurate understanding of ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2017, 362(3):405-412]

Cited: 8 times

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Lack of Influence of Substrate on Ligand Interaction with the Human Multidrug and Toxin Extruder, MATE1.

Lucy J Martínez-Guerrero, Mark Morales, Sean Ekins, Stephen H Wright,

Multidrug and toxin extruder (MATE) 1 plays a central role in mediating renal secretion of organic cations, a structurally diverse collection of compounds that includes ∼40% of prescribed drugs. Because inhibition of transport activity of other multidrug transporters, including the organic cation transporter (OCT) 2, is influenced by the structure ... Read more >>

Mol Pharmacol (Molecular pharmacology)
[2016, 90(3):254-264]

Cited: 4 times

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Making Transporter Models for Drug-Drug Interaction Prediction Mobile.

Sean Ekins, Alex M Clark, Stephen H Wright,

The past decade has seen increased numbers of studies publishing ligand-based computational models for drug transporters. Although they generally use small experimental data sets, these models can provide insights into structure-activity relationships for the transporter. In addition, such models have helped to identify new compounds as substrates or inhibitors of ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2015, 43(10):1642-1645]

Cited: 6 times

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Xenobiotic transporter expression along the male genital tract.

David M Klein, Stephen H Wright, Nathan J Cherrington,

The male genital tract plays an important role in protecting sperm by forming a distinct compartment separate from the body which limits exposure to potentially toxic substrates. Transporters along this tract can influence the distribution of xenobiotics into the male genital tract through efflux back into the blood or facilitating ... Read more >>

Reprod Toxicol (Reproductive toxicology (Elmsford, N.Y.))
[2014, 47:1-8]

Cited: 6 times

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SLC22, SLC44, and SLC47 transporters--organic anion and cation transporters: molecular and cellular properties.

Ryan M Pelis, Stephen H Wright,

Transporters within the SLC22, SLC44, and SLC47 families of solute carriers mediate transport of a structurally diverse array of organic electrolytes, that is, molecules that are generally charged (cationic, anionic, or zwitterionic) at physiological pH. Transporters in the SLC22 family--all of which are members of the major facilitator superfamily (MFS) ... Read more >>

Curr Top Membr (Current topics in membranes)
[2014, 73:233-261]

Cited: 22 times

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Localization of multidrug resistance-associated proteins along the blood-testis barrier in rat, macaque, and human testis.

David M Klein, Stephen H Wright, Nathan J Cherrington,

The blood-testis barrier (BTB) prevents the entry of many drugs into seminiferous tubules, which can be beneficial for therapy not intended for the testis but may decrease drug efficacy for medications requiring entry to the testis. Previous data have shown that some of the transporters in the multidrug resistance-associated protein ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2014, 42(1):89-93]

Cited: 10 times

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Basolateral uptake of nucleosides by Sertoli cells is mediated primarily by equilibrative nucleoside transporter 1.

David M Klein, Kristen K Evans, Rhiannon N Hardwick, William H Dantzler, Stephen H Wright, Nathan J Cherrington,

The blood-testis barrier (BTB) prevents the entry of many xenobiotic compounds into seminiferous tubules thereby protecting developing germ cells. Understanding drug transport across the BTB may improve drug delivery into the testis. Members of one class of drug, nucleoside reverse transcriptase inhibitors (NRTIs), do penetrate the BTB, presumably through interaction ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2013, 346(1):121-129]

Cited: 15 times

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Substrate-dependent inhibition of human MATE1 by cationic ionic liquids.

Lucy J Martínez-Guerrero, Stephen H Wright,

The multidrug and toxin extruders 1- and 2-K (MATE1 and MATE2-K) are expressed in the luminal membrane of renal proximal tubule cells and provide the active step in the secretion of molecules that carry a net positive charge at physiologic pH, so-called organic cations. The present study tested whether structurally ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2013, 346(3):495-503]

Cited: 22 times

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Substrate-dependent ligand inhibition of the human organic cation transporter OCT2.

Mathew Belzer, Mark Morales, Bhumasamudram Jagadish, Eugene A Mash, Stephen H Wright,

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 ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2013, 346(2):300-310]

Cited: 42 times

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Functional significance of conserved cysteines in the human organic cation transporter 2.

Ryan M Pelis, Yodying Dangprapai, Yaofeng Cheng, Xiaohong Zhang, Jennifer Terpstra, Stephen H Wright,

The significance of conserved cysteines in the human organic cation transporter 2 (hOCT2), namely the six cysteines in the long extracellular loop (loop cysteines) and C474 in transmembrane helix 11, was examined. Uptake of tetraethylammonium (TEA) and 1-methyl-4-phenypyridinium (MPP) into Chinese hamster ovary cells was stimulated >20-fold by hOCT2 expression. ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2012, 303(2):F313-20]

Cited: 6 times

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Molecular determinants of ligand selectivity for the human multidrug and toxin extruder proteins MATE1 and MATE2-K.

Bethzaida Astorga, Sean Ekins, Mark Morales, Stephen H Wright,

The present study compared the selectivity of two homologous transport proteins, multidrug and toxin extruders 1 and 2-K (MATE1 and MATE2-K), and developed three-dimensional pharmacophores for inhibitory ligand interaction with human MATE1 (hMATE1). The human orthologs of MATE1 and MATE2-K were stably expressed in Chinese hamster ovary cells, and transport ... Read more >>

J Pharmacol Exp Ther (The Journal of pharmacology and experimental therapeutics)
[2012, 341(3):743-755]

Cited: 39 times

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Interaction of H+ with the extracellular and intracellular aspects of hMATE1.

Yodying Dangprapai, Stephen H Wright,

Human multidrug and toxin extrusion 1 (hMATE1, SLC47A1) is a major candidate for being the molecular identity of organic cation/proton (OC/H(+)) exchange activity in the luminal membrane of renal proximal tubules. Although physiological function of hMATE1 supports luminal OC efflux, the kinetics of hMATE1-mediated OC transport have typically been characterized ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2011, 301(3):F520-8]

Cited: 11 times

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Renal transport of organic anions and cations.

Ryan M Pelis, Stephen H Wright,

Organic anions and cations (OAs and OCs, respectively) comprise an extraordinarily diverse array of compounds of physiological, pharmacological, and toxicological importance. The kidney, primarily the renal proximal tubule, plays a critical role in regulating the plasma concentrations of these organic electrolytes and in clearing the body of potentially toxic xenobiotics ... Read more >>

Compr Physiol (Comprehensive Physiology)
[2011, 1(4):1795-1835]

Cited: 24 times

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Characterization of the inhibitory effects of N-butylpyridinium chloride and structurally related ionic liquids on organic cation transporters 1/2 and human toxic extrusion transporters 1/2-k in vitro and in vivo.

Yaofeng Cheng, Lucy J Martinez-Guerrero, Stephen H Wright, Robert K Kuester, Michelle J Hooth, I Glenn Sipes,

Ionic liquids (ILs) are a class of salts that are expected to be used as a new source of solvents and for many other applications. Our previous studies revealed that selected ILs, structurally related organic cations, are eliminated exclusively in urine as the parent compound, partially mediated by renal transporters. ... Read more >>

Drug Metab Dispos (Drug metabolism and disposition: the biological fate of chemicals)
[2011, 39(9):1755-1761]

Cited: 6 times

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Differences in the substrate binding regions of renal organic anion transporters 1 (OAT1) and 3 (OAT3).

Bethzaida Astorga, Theresa M Wunz, Mark Morales, Stephen H Wright, Ryan M Pelis,

This study examined the selectivity of organic anion transporters OAT1 and OAT3 for structural congeners of the heavy metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS). Thiol-reactive reagents were also used to test structural predictions based on a homology model of OAT1 structure. DMPS was near equipotent in its ability to inhibit OAT1 ... Read more >>

Am J Physiol Renal Physiol (American journal of physiology. Renal physiology)
[2011, 301(2):F378-86]

Cited: 8 times

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Solution structure of the leader sequence of the patellamide precursor peptide, PatE1-34.

Wael E Houssen, Stephen H Wright, Arnout P Kalverda, Gary S Thompson, Sharon M Kelly, Marcel Jaspars,

The solution structure of the leader sequence of the patellamide precursor peptide was analysed by using CD and determined with NOE-restrained molecular dynamics calculations. This leader sequence is highly conserved in the precursor peptides of some other cyanobactins harbouring heterocycles, and is assumed to play a role in targeting the ... Read more >>

Chembiochem (Chembiochem : a European journal of chemical biology)
[2010, 11(13):1867-1873]

Cited: 17 times

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Membrane transporters in drug development.

, Kathleen M Giacomini, Shiew-Mei Huang, Donald J Tweedie, Leslie Z Benet, Kim L R Brouwer, Xiaoyan Chu, Amber Dahlin, Raymond Evers, Volker Fischer, Kathleen M Hillgren, Keith A Hoffmaster, Toshihisa Ishikawa, Dietrich Keppler, Richard B Kim, Caroline A Lee, Mikko Niemi, Joseph W Polli, Yuichi Sugiyama, Peter W Swaan, Joseph A Ware, Stephen H Wright, Sook Wah Yee, Maciej J Zamek-Gliszczynski, Lei Zhang,

Membrane transporters can be major determinants of the pharmacokinetic, safety and efficacy profiles of drugs. This presents several key questions for drug development, including which transporters are clinically important in drug absorption and disposition, and which in vitro methods are suitable for studying drug interactions with these transporters. In addition, ... Read more >>

Nat Rev Drug Discov (Nature reviews. Drug discovery)
[2010, 9(3):215-236]

Cited: 1343 times

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Organic anion transporter 3 (OAT3) and renal transport of the metal chelator 2,3-dimercapto-1-propanesulfonic acid (DMPS).

Matthias Rödiger, Xiaohong Zhang, Bernhard Ugele, Nikolaus Gersdorff, Stephen H Wright, Gerhard Burckhardt, Andrew Bahn,

Recent investigations involving intact rabbit renal proximal tubules indicated that organic anion transporter 3 (OAT3) may be involved in the transport of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Therefore, we evaluated the interaction of OAT3 with DMPS to determine the effect of OAT3 on basolateral DMPS uptake. We used stably transfected HEK293 cells ... Read more >>

Can J Physiol Pharmacol (Canadian journal of physiology and pharmacology)
[2010, 88(2):141-146]

Cited: 12 times

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