Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 26 (3), 115-117

Mechanistic Ligand-Receptor Interaction Model: Operational Model of Agonism


Mechanistic Ligand-Receptor Interaction Model: Operational Model of Agonism

Hyungsub Kim et al. Transl Clin Pharmacol.


This tutorial explains the basic principles of mechanistic ligand-receptor interaction model, which is an operational model of agonism. A growing number of agonist drugs, especially immune oncology drugs, is currently being developed. In this tutorial, time-dependent ordinary differential equation for simple Emax operational model of agonism was derived step by step. The differential equation could be applied in a pharmacodynamic modeling software, such as NONMEM, for use in non-steady state experiments, in which experimental data are generated while the interaction between ligand and receptor changes over time. Making the most of the non-steady state experimental data would simplify the experimental processes, and furthermore allow us to identify more detailed kinetics of a potential drug. The operational model of agonism could be useful to predict the optimal dose for agonistic drugs from in vitro and in vivo animal pharmacology experiments at the very early phase of drug development.

Keywords: Mechanistic ligand-receptor interaction; Operational model of agonism; Optimal dose; Prediction.

Conflict of interest statement

Conflicts of interests: Authors: The authors declare that they have no conflict of interests Reviewers: Nothing to declare Editors: Nothing to declare

Similar articles

See all similar articles


    1. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006;355:1018–1028. - PubMed
    1. Salahudeen MS, Nishtala PS. An overview of pharmacodynamics modelling, ligand-binding approach and its application in clinical practice. Saudi Pharm J. 2017;25:165–175. doi: 10.1016/j.jsps.2016.07.002. - DOI - PMC - PubMed
    1. Black JW, Leff P. Operational model of pharmacological agonism. Proc R Soc Lond B Biol Sci. 1983;220:141–162. - PubMed
    1. Black JW, Leff P, Shankley NP, Wood J. An operational model of pharmacological agonism: the effect of E/[A] curve shape on agonist dissociation constant estimation. Br J Pharmacol. 1985;84:561–571. - PMC - PubMed

LinkOut - more resources