Download Allosteric Function(s) of Proteins

Pharmacology in Drug Discovery I: Agonism and Efficacy
Terry Kenakin Ph.D., Dept Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC
Allosteric Function(s) of Proteins
March 31st -April 1st (2016)
March 31 st, 9 am-12:00 pm
Room 521 Meakins Auditorium
Course materials and Introduction
Theory of Allostery
Receptor Structure and Allosterism
Special properties of Allosteric Molecules
Studying Allosterism through Binding
March 31st, 1:30-4 pm
Room 504 Martin Auditorium
Quantification of Activity of Allosteric Molecules
NAMs, PAMs, SAMs, PAM-Antagonists
April 1st, 9 am-12:00 pm
Room 521 Meakins
Other Allosteric Targets: Nicotinic Receptors, Ion Channels, Enzymes'
Therapeutic Considerations for Allosteric Molecules
Course Review, Questions & Answers
April 1st, 1pm
Room 1345 McIntyre Medical Building
SEMINAR
A Perfect Storm comes to Pharmacology:
The Impact of Biased Signaling and Allostery on Drug Discovery
Abstract: Two major influences have entered Pharmacology over the past 15 years that have
revolutionized the discipline, especially in terms of how new drugs are discovered in industry and
academia. Specifically, ideas from molecular dynamics have reshaped receptor theory from the
rigid single-active state concepts prevalent historically into a modern view of dynamic protein
ensembles of multiple receptor active states. Second, the technology of pharmacological assays
has exploded to give experimenters many more views of receptor function. This, in turn, has
shown that receptor 'efficacy' is much more complex than previously thought and that drugs have
'efficacy fingerprints' comprised of many different efficacies. Hopefully this should allow us to
erode at the single most important reason for new drug failure since 2008, namely failure in
therapeutic efficacy (50% failure rate). These ideas will be illustrated through data for new
allosteric drugs and biased agonists.