Receptor Kinetics and Residence Time – What the Medicinal Chemist Needs to Know
Participants will be introduced to the fundamentals of time-dependent inhibition and how these factors can impact drug discovery and development. The course will cover a range of topics from an introduction to the basic principles, to practical methods for measuring and using time-dependent inhibition data, to the factors that determine the best use of these data to enable medicinal chemistry driven projects. Case studies, derived from the literature and ranging from lead discovery to marketed drugs, will be used to reinforce and provide real-world examples of the practical application of these concepts.
Topics to be covered include:
- Differences between open and closed systems
- Kinetic mechanisms driving time-dependent inhibition behavior
- Techniques to measure and utilize time-dependent inhibition data in drug discovery projects
- Examples demonstrating the impact of residence time data to advance lead series
Stewart L. Fisher, Ph.D., Principal, SL Fisher Consulting, LLC
Stewart Fisher received his Doctorate of Philosophy degree in Chemistry from the California Institute of Technology in 1993. After a post-doctoral fellowship at Harvard Medical School working on mechanisms of antibiotic resistance under the direction of Professor Christopher T. Walsh, Stewart spent two years at Hoffmann LaRoche working on obesity drug discovery research. In 1998, he returned to the Boston area to join AstraZeneca in the Infection Discovery Unit. During his 15 year tenure at AstraZeneca, he led several drug discovery projects that delivered candidates to Phase I clinical trials and ultimately served as Executive Director of the Infection Bioscience Department. Stewart is now the Principal at SL Fisher Consulting, LLC providing strategic advice in the areas of Infection Discovery and quantitative biochemistry. He has Visiting Scientist appointments at Stony Brook University and The Broad Institute and is a member of the Executive Council for The Protein Society.
Peter J. Tonge, Ph.D., Professor, Chemistry, Institute for Chemical Biology & Drug Discovery, Stony Brook University
Peter Tonge is a Professor of Chemistry and the Director of Infectious Disease Research in the Institute for Chemical Biology & Drug Discovery at Stony Brook University. He is also the Director of the Translational Experimental Therapeutics Laboratory in the School of Medicine. He received his Ph.D. from Birmingham University and was a SERC-NATO postdoctoral fellow at the NRC in Canada. Following positions at the NRC and the Picower Institute for Medical Research, he joined Stony Brook in 1996. His research program combines kinetic, structural, computational and biophysical approaches to develop inhibitors of enzyme drug targets. A primary focus of his program involves the rational optimization of drug-target residence time, based on the hypothesis that the life time of the drug-target complex is a critical factor for in vivo drug activity. Compounds with altered residence times are used to assess the impact of drug-target binding kinetics on in vivo drug activity and to inform on drug-target vulnerability. Correlations between drug PK and PD are aided by the development of radiotracers and the use of positron emission tomography to non-invasively image drug biodistribution.