• Publications
  • Influence
G Protein-Coupled Receptor Allosterism and Complexing
It is proposed that the study of allosteric phenomena will become of progressively greater import to the drug discovery process due to the advent of newer and more sensitive GPCR screening technologies.
Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules
GW9508 was able to potentiate the KCl‐mediated increase in insulin secretion in MIN6 cells and demonstrate that small‐molecule GPR40 agonists are glucose‐sensitive insulin secretagogues, adding further evidence to a link between G PR40 and the ability of fatty acids to acutely potentiate insulin secretion.
Seven Transmembrane Receptors as Shapeshifting Proteins: The Impact of Allosteric Modulation and Functional Selectivity on New Drug Discovery
These apparently diverse pharmacological effects of seven transmembrane receptors are discussed in terms of molecular dynamics and protein ensemble theory, which tends to unify 7TMR behavior toward cells.
A simple method for quantifying functional selectivity and agonist bias.
A scale based on the Black and Leff operational model that contains the key elements required to describe 7TM agonism, namely, affinity for the receptor and efficacy in activating a particular signaling pathway, can statistically evaluate selective agonist effects in a manner that can theoretically inform structure-activity studies and/or drug candidate selection matrices.
International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on Terms and Symbols in Quantitative Pharmacology
The recommendations that follow have been updated from the proposals of a Technical Subcommittee set up by the International Union of Pharmacology Committee on Receptor Nomenclature and Drug
Signalling bias in new drug discovery: detection, quantification and therapeutic impact
A viewpoint on which methods are appropriate for quantifying bias is provided, based on knowledge of how cellular and intracellular signalling proteins control the conformation of seven-transmembrane receptors.
The CCR5 Receptor-Based Mechanism of Action of 873140, a Potent Allosteric Noncompetitive HIV Entry Inhibitors⃞
4-{[4-({(3R)-1-Butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5dioxo-1,4,9-triazaspiro]oxy}benzoic acid hydrochloride (873140) is a potent noncompetitive allosteric antagonist of the CCR5 receptor with concomitantly potent antiviral effects for HIV-1.
Inverse, protean, and ligand‐selective agonism: matters of receptor conformation
  • T. Kenakin
  • Biology
    FASEB journal : official publication of the…
  • 1 March 2001
Evidence for the existence of the various types of agonism and the potential therapeutic utility of differ¬ent agonist types is reviewed.