The New World of Allosteric Modulation: A Dimmer Switch for GPCR Agonism and Antagonism
GPCRs are nature’s prototypical allosteric protein and all functions of these proteins involve the transduction of ligand induced conformational change to a third body (i.e. signaling protein, other ligand). There are new ligand properties that can be determined through the application of allosteric theory to GPCRs that can greatly expand knowledge and predictability of drug candidate effects. One of the main properties is probe dependence whereby GPCRs are now seen not to be mere switches but rather microprocessors that can receive different signals in and yield different signals out to the cell.
In this webinar, we will cover:
- What is unique about designing allosteric modulators and how they modulate GPCR activity by acting as a dimmer switch
- Case studies of how Eurofins Pharma Discovery Services can be used for characterizing positive and negative allosteric modulators in scales amenable to medicinal chemistry modification.
- Assessing probe dependence in the form of biased agonist signaling and induced bias for PAMs and NAMs.
Presented by Professor Terry Kenakin
Department of Pharmacology, University of North Carolina School of Medicine
After receiving a BSc in Chemistry and Ph.D. in Pharmacology from the University of Alberta and a post doctoral Fellowship at University College, London, Dr. Kenakin worked in drug discovery at Burroughs-Wellcome (7 yr) and GlaxoSmithKline (25 yrs) before joining the UNC School of Medicine in 2011. His work has been focused on drug receptor theory and allosteric protein function.