David Roche, Debora Gil, & Jesus Giraldo. (2012). Assessing agonist efficacy in an uncertain Em world. In A. Christopoulus and M. Bouvier (Ed.), 40th Keystone Symposia on mollecular and celular biology (79). Keystone Symposia.
Abstract: The operational model of agonism has been widely used for the analysis of agonist action since its formulation in 1983. The model includes the Em parameter, which is defined as the maximum response of the system. The methods for Em estimation provide Em values not significantly higher than the maximum responses achieved by full agonists. However, it has been found that that some classes of compounds as, for instance, superagonists and positive allosteric modulators can increase the full agonist maximum response, implying upper limits for Em and thereby posing doubts on the validity of Em estimates. Because of the correlation between Em and operational efficacy, τ, wrong Em estimates will yield wrong τ estimates.
In this presentation, the operational model of agonism and various methods for the simulation of allosteric modulation will be analyzed. Alternatives for curve fitting will be presented and discussed.