TS1: TARGETING GPCRs FOR DRUG DISCOVERY

NEW DATES - TUESDAY, AUGUST 25 - WEDNESDAY, AUGUST 26
DAY 1: 8:00 AM - 7:00 PM | DAY 2: 7:30 AM - 12:00 PM

DAY 1: TUESDAY ALL DAY
Follows schedule of main event, including refreshment breaks in exhibit hall for poster viewing and networking
Lunch Provided
Plenary Keynote Session
Welcome Cocktail Reception

DAY 2: WEDNESDAY MORNING
Follows schedule of main event, including refreshment breaks in exhibit hall for poster viewing and networking
Breakfast Breakout Discussions

About this Training Seminar: This training seminar is designed for medicinal chemists, biologists, and scientists concentrating on discovering and developing drugs against G protein-coupled receptors (GPCRs). The challenge the seminar addresses is how to predict therapeutic activity – because drug candidate profiles seen in in vitro test systems often do not adequately reflect in vivo responses due to the drug candidates’ interaction with variable ambient physiology. More specifically, this seminar describes the pharmacological procedures needed to convert ‘descriptive data’ (what we see) to ‘predictive data’ (what will be seen) through universal pharmacological scales, such as affinity, efficacy, cooperativity parameters, offset rates, etc. The desired outcome is to more fully define ligand properties to reduce attrition in late-stage drug development. Three major classes of GPCR ligands will be discussed: (1) agonists (with special reference to biased signaling); (2) antagonists (with inverse agonists); and (3) allosteric modulators (characterization of NAMs, PAMs). I will illustrate how concepts introduced over the past 15 years have considerably expanded and revitalized the possibilities for GPCRs as therapeutic targets.

Topics to be covered in the seminar:

• How to measure the 4 Main Universal Activity Parameters for Drugs:
  • What is the affinity of the molecule for the target?
  • What changes in target behavior are produced upon binding (i.e. efficacies)?
  • Does the endogenous ligand interact with the target in an orthosteric or allosteric manner?
  • What is the rate of offset from the target (in vivo target coverage)?
• Strengths and weaknesses of functional, binding assays, and kinetic assays
• Agonists: affinity vs. efficacy: biased agonist signaling and how to use it for drug development
• Antagonists: affinity vs. efficacy (positive or inverse agonism), non-competitive, irreversible, and hemi-equilibria
• Constitutive activity: inverse agonism and its relevance
• Allosterism: binding models, parameters for characterizing agonists, antagonists, PAMs, NAMs, and NAM antagonists

Instructor Biography:
Terry Kenakin, PhD, Professor, Department of Pharmacology, University of North Carolina School of Medicine
Beginning his career as a synthetic chemist, Terry Kenakin received a PhD in Pharmacology at the University of Alberta in Canada. After a postdoctoral fellowship at University College London, UK, he joined Burroughs-Wellcome as an associate scientist for 7 years. From there, he continued working in drug discovery for 25 years first at Glaxo, Inc., then Glaxo Wellcome 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.

Training Seminar Information

Each CHI Training Seminar offers 1.5 days of instruction with start and stop times for each day shown above and on the Event-at-a-Glance published in the onsite Program & Event Guide. Training Seminars will include morning and afternoon refreshment breaks, as applicable, and lunch will be provided to all registered attendees on the full day of the class.

Each person registered specifically for the Training Seminar will be provided with a hard copy handbook for the seminar in which they are registered. A limited number of additional handbooks will be available for other delegates who wish to attend the seminar, but after these have been distributed, no additional books will be available.

Though CHI encourages track hopping between conference programs, we ask that Training Seminars not be disturbed once they have begun. In the interest of maintaining the highest quality learning environment for Training Seminar attendees, and because seminars are conducted differently than conference programming, we ask that attendees commit to attending the entire program, and not engage in track hopping, as to not disturb the hands-on style instruction being offered to the other participants.