Receptor Antagonism: Data Driven Approaches to Measuring Receptor Blockade

March 4, 2011
1:00 pm – 2:30 pm EST



Two types of receptor antagonist mechanism will be discussed: steric hindrance and allosteric modulation. Methods to quantify the affinity of orthosteric antagonists producing competitive and non-competitive antagonism will be described and the emerging therapeutic importance of allosteric modulation will be highlighted. Methods to detect allosteric and quantify allosteric effects from antagonism to potentiation of agonist response will be discussed. The importance of receptor offset rates will be considered in terms of therapeutic target coverage along with methods to measure antagonist kinetics of offset.

Learning Objective Bullet Points:

  • This session is designed to solve a problem, namely the use of in vitro antagonism data to identify antagonism mechanism of action and through this, to use the correct model to accurately estimate the affinity of the antagonist for the target.
  • Students also will learn the important distinctions between orthosteric and allosteric antagonists and the methods to differentiate these two mechanisms
  • The allosteric discussion will extend to potentiators of agonism (PAMs, positive allosteric modulators); the design of screens and assays needed to quantify allosterism will be described.


Who Should Attend:

  • Any biological scientist dealing with dose-response data in integrated systems (pharmacologists, biochemists, enzymologists)
  • Medicinal chemists who must understand dose-response data


Instructor Information: 
Terry KenakinTerry Kenakin Ph.D.
Professor, Department of Pharmacology
University of North Carolina School of Medicine
Chapel Hill NC

Instructor Biography:
Terrence Kenakin, Ph.D., is Professor in the Department of Pharmacology, University of North Carolina, Chapel Hill. Until August of 2011, Dr. Kenakin was director of research at GlaxoSmithKline Research and Development laboratories at Research Triangle Park, NC where he optimized drug activity assay systems for the discovery and testing of. allosteric molecules mostly for the treatment of diabetes. Before starting the major stint of his drug discovery career at GSK, Dr. Kenakin was an associate scientist at Burroughs-Wellcome in the U.K. which he joined after a post-doctoral fellowship at University College London, U.K. Dr. Kenakin earned his Ph.D. in Pharmacology at the University of Alberta, Edmonton Canada.

Dr. Kenakin is a member of many editorial boards as well as Co-editor-in-Chief of the Journal of Receptors and Signal Transduction. In addition, he has authored numerous articles and has written eight books on pharmacology, including the popular "A Pharmacology Primer".

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