Research Topics
| Steven J CharltonSummaryAffiliation: Novartis Institutes for BioMedical Research Publications
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Detail Information
Publications
The Influence of Receptor Kinetics on the Onset and Duration of Action and the Therapeutic Index of NVA237 and TiotropiumDavid A Sykes
Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom
J Pharmacol Exp Ther 343:520-8. 2012....
Elusive equilibrium: the challenge of interpreting receptor pharmacology using calcium assaysSteven J Charlton
Novartis Institutes for BioMedical Research, Horsham, UK
Br J Pharmacol 161:1250-65. 2010..LINKED ARTICLES: This article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2010.161.issue-6...- Agonist efficacy and receptor desensitization: from partial truths to a fuller pictureSteven J Charlton
Novartis Institutes for BioMedical Research, Horsham, UK
Br J Pharmacol 158:165-8. 2009..These findings challenge the notion that high-efficacy ligands always cause more functional desensitization... 
Miniaturized receptor binding assays: complications arising from ligand depletionClare M Scaramellini Carter
Novartis Institutes for BioMedical Research, West Sussex, UK
J Biomol Screen 12:255-66. 2007..In addition to those previously described by others, the authors propose a simple method capable of correcting errors in competition binding experiments performed in conditions of ligand depletion...- An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterolDavid Beattie
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom
Bioorg Med Chem Lett 22:6280-5. 2012.... - The identification of indacaterol as an ultralong-acting inhaled beta2-adrenoceptor agonistFrancois Baur
Respiratory Diseases Area, Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK
J Med Chem 53:3675-84. 2010..Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate... - Exploring the mechanism of agonist efficacy: a relationship between efficacy and agonist dissociation rate at the muscarinic M3 receptorDavid A Sykes
Novartis Institutes for BioMedical Sciences, Wimblehurst Road, Horsham, West Sussex, UK
Mol Pharmacol 76:543-51. 2009..These data suggest that kinetic models incorporating the mean lifetime of specific complexes will be required to fully explain the nature of agonist efficacy... - A physical properties based approach for the exploration of a 4-hydroxybenzothiazolone series of beta2-adrenoceptor agonists as inhaled long-acting bronchodilatorsDavid Beattie
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom
Bioorg Med Chem Lett 20:5302-7. 2010..This approach identified beta-phenethyl, alpha-substituted cyclopentyl and monoterpene N-substituents to be of particular interest for further evaluation, as exemplified by structures 19, 29 and 33, respectively... - Quantifying the association and dissociation rates of unlabelled antagonists at the muscarinic M3 receptorMark R Dowling
Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB
Br J Pharmacol 148:927-37. 2006.... - Slow receptor dissociation is not a key factor in the duration of action of inhaled long-acting β2-adrenoceptor agonistsDavid A Sykes
Novartis Institutes for BioMedical Research, West Sussex, UK
Br J Pharmacol 165:2672-83. 2012..We have investigated whether the receptor binding kinetics of β(2) -adrenoceptor agonists can explain their observed onset of action and duration of effect in the clinic... - Measuring receptor target coverage: a radioligand competition binding protocol for assessing the association and dissociation rates of unlabeled compoundsDavid A Sykes
Novartis Institutes for BioMedical Research, Horsham, West Sussex, United Kingdom
Curr Protoc Pharmacol . 2010..The protocol described in this unit is a kinetic radioligand competition binding assay that makes possible the determination of both the association and dissociation rates of unlabeled receptor ligands... - ATP priming of macrophage-derived chemokine responses in CHO cells expressing the CCR4 receptorElizabeth M Rosethorne
Novartis Horsham Research Centre, Wimblehurst Road, RH12 5AB, UK
Naunyn Schmiedebergs Arch Pharmacol 370:64-70. 2004..In conclusion, pre-stimulation of endogenous P2Y receptors with ATP facilitates Ca2+ signalling at the recombinant CCR4 receptor in CHO cells, although the mechanism by which this occurs remains to be defined... - In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of actionCliff Battram
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom
J Pharmacol Exp Ther 317:762-70. 2006.... - Efficacy is a contributing factor to the clinical onset of bronchodilation of inhaled beta(2)-adrenoceptor agonistsElizabeth M Rosethorne
Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, UK
Naunyn Schmiedebergs Arch Pharmacol 382:255-63. 2010..We have demonstrated that the rate of cAMP accumulation is influenced by agonist efficacy and that this, in combination with lipophilicity, may explain why beta(2) AR agonists demonstrate differences in their onset of action... - Synthesis and evaluation of two series of 4'-aza-carbocyclic nucleosides as adenosine A2A receptor agonistsDavid Beattie
Novartis Institutes for BioMedical Research, Respiratory Diseases Area, Horsham, United Kingdom
Bioorg Med Chem Lett 20:1219-24. 2010..The propionamides 14-18 and the 4-hydroxymethylpyrazole 32 were determined to be the most potent and selective examples from the 4'-reversed amide and 4'-N-bonded heterocyclic series, respectively... - The in vitro metabolism of sphingosine-1-phosphate: identification; inhibition and pharmacological implicationsMichelle E Bradley
Novartis Institutes for BioMedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB, UK
Eur J Pharmacol 672:56-61. 2011..In the absence of sodium orthovanadate, it is envisaged that experiments involving exogenously applied S1P to broken cell preparations, whole cells or tissues, coupled with long incubation times will be subjected to metabolism... - Agonist-biased signaling at the histamine H4 receptor: JNJ7777120 recruits β-arrestin without activating G proteinsElizabeth M Rosethorne
Novartis Institutes for BioMedical Research, Horsham, West Sussex, UK
Mol Pharmacol 79:749-57. 2011..In conclusion, we have demonstrated that JNJ7777120 recruits β-arrestin to the H(4) receptor, independent of G protein activation... - Assessing the minimum number of data points required for accurate IC50 determinationRobert J Turner
Novartis Institutes for BioMedical Research, Horsham, UK
Assay Drug Dev Technol 3:525-31. 2005..89). This study shows that it is possible to generate IC50 values from an appropriately designed primary inhibition screen using two compound concentrations, reducing the requirement for follow-up IC50 determinations...