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All Outputs (21)

Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2 (2023)
Journal Article

The inhibition of CXC chemokine receptor 2 (CXCR2), a key inflammatory mediator, is a potential strategy in the treatment of several pulmonary diseases and cancers. The complexity of endogenous chemokine interaction with the orthosteric binding site... Read More about Design, Synthesis, and Application of Fluorescent Ligands Targeting the Intracellular Allosteric Binding Site of the CXC Chemokine Receptor 2.

Investigating the Influence of Tracer Kinetics on Competition-Kinetic Association Binding Assays: Identifying the Optimal Conditions for Assessing the Kinetics of Low-Affinity Compounds (2019)
Journal Article

An increased appreciation of the importance of optimizing drug-binding kinetics has lead to the development of various techniques for measuring the kinetics of unlabeled compounds. One approach is the competition-association kinetic binding method fi... Read More about Investigating the Influence of Tracer Kinetics on Competition-Kinetic Association Binding Assays: Identifying the Optimal Conditions for Assessing the Kinetics of Low-Affinity Compounds.

Pharmacological characterization of a novel 5-hydroxybenzothiazolone-derived b2-adrenoceptor agonist with functional selectivity for anabolic effects on skeletal muscle resulting in a wider cardiovascular safety window in preclinical studies (2019)
Journal Article

Copyright ª 2019 by The Author(s) The anabolic effects of b2-adrenoceptor (b2-AR) agonists on skeletal muscle have been demonstrated in various species. However, the clinical use of b2-AR agonists for skeletal muscle wasting conditions has been limit... Read More about Pharmacological characterization of a novel 5-hydroxybenzothiazolone-derived b2-adrenoceptor agonist with functional selectivity for anabolic effects on skeletal muscle resulting in a wider cardiovascular safety window in preclinical studies.

Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations (2018)
Journal Article

G protein–coupled receptors (GPCRs) are the largest class of cell surface signaling proteins, participate in nearly all physiological processes, and are the targets of 30% of marketed drugs. Typically, nanomolar to micromolar concentrations of ligand... Read More about Preassembled GPCR signaling complexes mediate distinct cellular responses to ultralow ligand concentrations.

The inhibition of human lung fibroblast proliferation and differentiation by Gs-coupled receptors is not predicted by the magnitude of cAMP response (2018)
Journal Article

Background Idiopathic pulmonary fibrosis (IPF) is 22 a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel t... Read More about The inhibition of human lung fibroblast proliferation and differentiation by Gs-coupled receptors is not predicted by the magnitude of cAMP response.

Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors (2017)
Journal Article

Atypical antipsychotic drugs (APDs) have been hypothesized to show reduced extrapyramidal side effects (EPS) due to their rapid dissociation from the dopamine D2 receptor. However, support for this hypothesis is limited to a relatively small number o... Read More about Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors.

Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma (2017)
Journal Article

Further optimization of an initial DP2 receptor antagonist clinical candidate NVPQAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2- (trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11,... Read More about Discovery of fevipiprant (NVP-QAW039), a potent and selective DP2 receptor antagonist for treatment of asthma.

Uncoupling the Structure–Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding (2016)
Journal Article

Ligand binding to membrane proteins may be significantly influenced by the interaction of ligands with the membrane. In particular, the microscopic ligand concentration within the membrane surface solvation layer may exceed that in bulk solvent, resu... Read More about Uncoupling the Structure–Activity Relationships of β2 Adrenergic Receptor Ligands from Membrane Binding.

Fevipiprant (QAW039), a slowly dissociating CRTh2 antagonist with the potential for improved clinical efficacy (2016)
Journal Article

Here we describe the pharmacologic properties of a series of clinically relevant chemoattractant receptor-homologous molecules expressed on T-helper type 2 (CRTh2) receptor antagonists, including fevipiprant (NVP-QAW039 or QAW039), which is currently... Read More about Fevipiprant (QAW039), a slowly dissociating CRTh2 antagonist with the potential for improved clinical efficacy.

Long receptor residence time of C26 contributes to super agonist activity at the human ?2 adrenoceptor (2016)
Journal Article

Super agonists produce greater functional responses than endogenous agonists in the same assay, and their unique pharmacology is the subject of increasing interest and debate. We propose that receptor residence time and the duration of receptor signa... Read More about Long receptor residence time of C26 contributes to super agonist activity at the human ?2 adrenoceptor.

Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins (2015)
Journal Article

© 2015 The British Pharmacological Society. Background and Purpose Plasma protein binding (PPB) influences the free fraction of drug available to bind to its target and is therefore an important consideration in drug discovery. While traditional meth... Read More about Simulating the influence of plasma protein on measured receptor affinity in biochemical assays reveals the utility of Schild analysis for estimating compound affinity for plasma proteins.

'Partial' competition of heterobivalent ligand binding may be mistaken for allosteric interactions: a comparison of different target interaction models (2014)
Journal Article

© 2014 The British Pharmacological Society. Background and Purpose Non-competitive drugs that confer allosteric modulation of orthosteric ligand binding are of increasing interest as therapeutic agents. Sought-after advantages include a ceiling level... Read More about 'Partial' competition of heterobivalent ligand binding may be mistaken for allosteric interactions: a comparison of different target interaction models.

Potent and efficacious inhibition of CXCR2 signaling by biparatopic nanobodies combining two distinct modes of action (2014)
Journal Article

Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics. Chemokines and chemokine receptors are key modulators in inflammatory diseases and malignancies. Here, we describe the identification and pharmacologic character... Read More about Potent and efficacious inhibition of CXCR2 signaling by biparatopic nanobodies combining two distinct modes of action.

Observed drug-receptor association rates are governed by membrane affinity: The importance of establishing "micro-pharmacokinetic/pharmacodynamic relationships" at the ?2-adrenoceptor (2014)
Journal Article

Current pharmacological models for determining affinity and kinetics of drugs for membrane receptors assume the interacting molecules are homogeneously distributed in the bulk aqueous phase. The phospholipid membrane can, however, provide a second co... Read More about Observed drug-receptor association rates are governed by membrane affinity: The importance of establishing "micro-pharmacokinetic/pharmacodynamic relationships" at the ?2-adrenoceptor.