Over the past 6 six years, the primary cause of new drug candidate failures (50%) has been failure of therapeutic efficacy. Put another way, drug discovery programs do everything right, get the defined candidate molecule, only to have it fail in therapeutic
trials. Among the most prevalent reasons proposed for this shortcoming is the lack of translation of in vitro and recombinant drug activity to therapeutic in vivo whole systems. Drug
activity in complete systems can be characterized with the application of pharmacological principles which translate drug behaviors in various organs with molecular scales of affinity and efficacy.
Pharmacological techniques are unique in that they can convert descriptive data (what we see, potency, activity in a given system) to predictive data (molecular scales of activity that can be used to predict activity in all systems including the therapeutic
one, i.e. affinity, efficacy). The predicted outcome of this process is a far lower failure rate as molecules are progressed toward clinical testing.
This course will describe pharmacological principles and procedures to quantify affinity, efficacy, biased signaling and allostery to better screen for new drugs and characterize drug candidates in lead optimization assays. In particular, new concepts
that have entered the fabric of discovery over the past few years, namely biased signaling and allosteric drug function, will be emphasized as new ways forward to reduce new candidate attrition in the drug discovery process.
Day 1 PM:
1. New Drug Discovery Infrastructure: Strategies- vs Target- vs Systems-Based, Discovery Teams, Target Selection
2. Cellular Activation (agonism): Affinity and
Efficacy, Potency, Biased Signaling, Selectivity, Screening for Agonists
Day 2 AM:
3. Antagonism: Orthosteric (competitive, non-competitive, hemi-equilibria), Partial Agonism, Screening for Antagonists
4. Inverse Agonism
5.
Allosteric Modulation, PAMs, NAMs, Screening for Allosterics
6. Candidate Selection: Real Time Kinetics and in vivo Target Coverage
Day 2 PM: Drug Development
7. Pharmacokinetics: Druglike Character, in vivo Absorption, Distribution, Metabolism
8. Excretion, in vivo PK, Non-Linear PK
9.
Safety Pharmacology: Safety vs Toxicity Risk Benefit Analyses
Instructor Bio:
Terry Kenakin, Ph.D., Professor, Department of Pharmacology, University of North Carolina School of Medicine
Dr. Kenakin has 32 years of experience in drug industry (7 at Burroughs-Wellcome and 25 at GlaxoSmithKline) as a project leader and lead optimization pharmacologist. The course is based on the book: A Pharmacology Primer: Techniques for more Effective
and Strategic Drug Discovery’ written by the instructor (Elsevier/Academic Press, 4th edition, 2014, pp 1-450). Summary sheets, exercises with answers, relevant papers will be provided to students, as well as a pdf of all presentation slides.
Course Material: Summary sheets, exercises with answers, relevant papers are included as well as a pdf of allslides. The course is based on the book A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery. 4th Edition, Elsevier/Academic Press, 2014.
The table of contents of this book can be viewed at: www.amazon.com/Pharmacology‐Primer‐Fourth‐Edition‐Techniques/
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.
