SC6: Introduction to Allosteric Modulators and Biased Ligands of GPCRs

After an introduction which discusses course resources (students will all receive electronic copies of the instructors 2 books on Pharmacology and Drug Discovery) a brief discourse on ‘what is allostery?’ will begin the lecture. Then we move on to allosteric modulators of GPCRs and special properties of allosteric modulators (i.e. PAMs, NAMs etc). Three important aspects of receptor-based allostery will then be discussed (Oligomerization, Agonism, 3-body Guest Allostery) as well as how allosterism can be studied with binding and functional experiments. The course ends with discussion of allosteric screening, methods to detect allostery and proof of allosteric mechanisms.

  • Overview of allosteric modulators and pathway biased ligands
  • Approaches for screening and validation
  • Fitting functional allosteric data to obtain allosteric drug parameters


SC_Terry_KenakinTerry Kenakin, PhD, Professor, Department of Pharmacology, University of North Carolina School of Medicine

Beginning his career as a synthetic chemist, Terry Kenakin received a Ph.D. in Pharmacology at the University of Alberta in Canada. After a post-doctoral fellowship at University College London, U.K., he joined Burroughs-Wellcome as an associate scientist (7 yrs). From there, he continued working in drug discovery for 25 years first at Glaxo Inc., then GlaxoWellcome and finally as a Director at GlaxoSmithKline Research and Development laboratories at Research Triangle Park, North Carolina, USA. Dr. Kenakin is now a professor in the Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill. Currently he is engaged in studies aimed at the optimal design of drug activity assays systems, the discovery and testing of allosteric molecules for therapeutic application and the quantitative modeling of drug effects. In addition, he is Director of the Pharmacology graduate courses at the UNC School of Medicine. He is a member of numerous editorial boards as well as editor in Chief of the Journal of Receptors and Signal Transduction. He has authored numerous articles and has written 10 books on Pharmacology.