Quantifying biased agonism: Understanding the links between affinity and efficacy

Nature Reviews Drug Discovery

Volumn 12, Issue 6, 2013, Pages 483-

  Rajagopal, Sudarshan ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR;

BINDING AFFINITY; BINDING ASSAY; COMPLEX FORMATION; DRUG RECEPTOR BINDING; LETTER; LIGAND BINDING; MATHEMATICAL MODEL; MOLECULAR INTERACTION; MOLECULAR MODEL; PREDICTION; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; ANIMAL; DRUG DEVELOPMENT; HUMAN; NOTE; PHYSIOLOGY;

ANIMALS; DRUG DISCOVERY; HUMANS; SIGNAL TRANSDUCTION;

EID: 84880663464     PISSN: 14741776     EISSN: 14741784     Source Type: Journal    
DOI: 10.1038/nrd3954-c1     Document Type: Letter

References (10)

1. Kenakin, T. & Christopoulos, A. Signalling bias in new drug discovery: detection, quantification and therapeutic impact. Nature Rev. Drug Discov. 12, 205-216 (2013).
2. Ariens, E. J. Affinity and intrinsic activity in the theory of competitive inhibition. I. Problems and theory. Arch. Int. Pharmacodyn. Ther. 99, 32-49 (1954).
3. Stephenson, R. P. A modification of receptor theory. Br. J. Pharmacol. Chemother. 11, 379-393 (1956).
4. Furchgott, R. F. in Advances in Drug Research (eds Harper, N. J. & Simmonds, A. B.) 21-55 (Academic Press, 1966).
5. Black, J. W. & Leff, P. Operational models of pharmacological agonism. Proc. R. Soc. Lond. B Biol. Sci. 220, 141-162 (1983).
6. De Lean, A., Stadel, J. M. & Lefkowitz, R. J. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled β-adrenergic receptor. J. Biol. Chem. 255, 7108-7117 (1980).
7. Samama, P., Cotecchia, S., Costa, T. & Lefkowitz, R. J. A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J. Biol. Chem. 268, 4625-4636 (1993).
8. Weiss, J. M., Morgan, P. H., Lutz, M. W. & Kenakin, T. P. The cubic ternary complex receptor-occupancy model. III. Resurrecting efficacy. J. Theor. Biol. 181, 381-397 (1996).
9. Rajagopal, S. et al. Quantifying ligand bias at seven-transmembrane receptors. Mol. Pharmacol. 80, 367-377 (2011).
10. Kenakin, T. et al. A simple method for quantifying functional selectivity and agonist bias. ACS Chem. Neurosci. 3, 193-203 (2012).