Pharmacological Target Engagement and Validation

With the advent of high-throughput, structure-assisted and virtual screening, an argument could be made that every target is now druggable. However, with an estimated 600-1500 possible druggable genes related to disease, the bottleneck now is judicious target choice; coupled with this is the choice of discovery strategy (target- vs system-based). This course discusses the pharmacological techniques available to relate targets to therapeutic opportunity, applications of new ideas to re-visit mined out or apparently intractable targets, validation beyond targets (pathway-validation) and strategies to improve the disappointing 50% efficacy failure rate for new drug candidates. 

Who Should Attend?

• Biologists involved in drug discovery
• Medicinal chemists
• Students of pharmacology
• Academic pharmacologists

Course Benefits

• Gain new insights into state of the art ideas on drug targets and their association with therapeutic opportunities
• Learn about new tools that quantitatively assess molecular effects on drug targets
• Learn how parameters from these methods can predict activity in all systems
• Define new vistas around old targets to better define chemical targets for receptors

Course Topics

• Systems vs Target-Based Research
• Validation - Example of CCR5 HIV
• Knock outs / Knock ins / DREADs
• Drugging Orphans - Current Methods
• Drugability vs. Target Choice
• 50% Efficacy Failures: Reasons Why / Ways Forward
• Target vs. Pathway Validation: biased signaling
• Single vs. Multiple Target Engagement (CNS Multi-Target Drugs)
• Target Remits (Criteria for New Drugs)
• Prosecuting the Genome (Single Genes vs ‘Nomic’ Collections)
• Drug ‘Re-Purposing’ / ‘Mined-Out’ or ‘Intractable’ Targets: Other Shots on Goal
• Virtual Screening / Conventional HTS

Instructor

Terry Kenakin, Ph.D.
UNC School of Medicine, Chapel Hill, NC

After obtaining a B.S. in chemistry and Ph.D. in Pharmacology at the University of Alberta, Dr. Kenakin worked for three years at University College London UK with Sir James Black. From there he spent 32 years in industry (Sever at Burroughs-Wellcome, 25 at GlaxoSmithKline). He is currently a Professor at the University of North Carolina School of Medicine. His interests have always been in quantitative pharmacodynamics and the discovery of new drugs and he has worked on projects for AIDS, heart failure and metabolic diseases. He is editor and chief of Journal of Receptors and Signal Transduction, and co-Editor in Chief of Current Opinion in Pharmacology. He has written 12 books on pharmacology.