Have many estimates of efficacy and affinity been misled? Revisiting the operational model of agonism.

Autor: Roche D; Laboratory of Molecular Neuropharmacology and Bioinformatics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain., van der Graaf PH; Division of Pharmacology, Cluster Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden, The Netherlands; Certara, Simcyp QSP, Canterbury Innovation Centre, Canterbury CT2 7FG, UK., Giraldo J; Laboratory of Molecular Neuropharmacology and Bioinformatics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain. Electronic address: Jesus.Giraldo@uab.es.
Jazyk: angličtina
Zdroj: Drug discovery today [Drug Discov Today] 2016 Nov; Vol. 21 (11), pp. 1735-1739. Date of Electronic Publication: 2016 Jun 24.
DOI: 10.1016/j.drudis.2016.06.019
Abstrakt: The operational model of agonism offers a general equation to account for steep or flat functional curves by including a slope parameter different from 1. However, because this equation is not a Hill equation, those steep or flat experimental curves that follow the Hill model are excluded from the operational framework. This conceptual omission could have significant consequences in the estimation of affinity and efficacy - the operational model tends to overestimate agonist-receptor dissociation constants and operational efficacy parameters to accommodate the shape of theoretical curves to steep or flat experimental Hill curves. To avoid misled parameter estimates for an ample space of pharmacological data a new version of the operational model has been developed.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: