PRE-CONFERENCE DINNER SHORT COURSES | September 25, 6:30-9:00 pm
Recent breakthroughs in obtaining high-resolution structures of G Protein-Coupled Receptors (GPCRs) are rapidly impacting the pharmaceutical industry. This course will review how newly elucidated GPCR crystal structures have informed our current understanding of GPCR function. The instructors will explore how this new structural information is guiding rational drug design approaches for targeting GPCRs. This course will also review the role of conformational dynamics in GPCR function and structural biology techniques for studying the conformational dynamics of GPCRs, including the burgeoning field of applying nuclear magnetic resonance (NMR) to study GPCR structure and dynamics.
Matthew Eddy, Ph.D., Postdoctoral Fellow, Ray Stevens Laboratory, The Bridge Institute, University of Southern California
Huixian Wu, Ph.D., Senior Scientist, Groton Center of Chemistry, Pfizer
Ion channels are important therapeutic targets and currently represent the second largest target class addressed by therapeutic drugs. Significant opportunities exist for targeting ion channels with antibodies, but to date, it has been challenging to discover therapeutic antibodies against them. This course will examine emerging technologies and strategies for enabling the isolation of functional anti-ion channel antibodies and highlight progress via case studies. The topics to be covered include: 1) Antibody discovery, including methods to generate monoclonal antibodies and antigen preparation strategies, 2) Assays to enable isolation of binding antibodies, including use of recombinant stable cell lines, 3) in vitro assays to measure functional activity of the antibody, including use of electrophysiology platforms and ion flux methods, and 4) Review of promising ligand-gated and voltage-gated ion channel targets and antibodies in development.
Trevor Wilkinson, Ph.D., Associate Director, Antibody Discovery and Protein Engineering, MedImmune Ltd., United Kingdom
The course will cover the design principles of covalent fragment libraries, target-based and phenotypic screens using covalent fragments, strategies to grow fragments into drug leads, and case studies. Topics to be covered include design principles of covalent fragment libraries, target-based and phenotypic screens using covalent fragments and current technologies to conduct those screens, strategies and considerations to grow covalent fragments into drug leads, coupling covalent fragment growth with selectivity profiling in cells, using covalent fragments as toolkits to discover novel drug targets in phenotypic screens, and photocrosslinking methods to identify fragment drug targets in cells.
Alexander Statsyuk, Ph.D., Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston
DINNER SHORT COURSES | September 27, 7:00-9:30 pm
In recent years, the understanding of both the immunotherapy and epigenetics of cancer has increased. This course will provide some details of how immunotherapy and epigenetic pathways interact and how they can be exploited to enhance the efficacy of current cancer treatments. The instructors will review recent scientific evidence and preclinical data that support the development of combination therapies and offer their perspectives on challenges that may have to be tackled along the way.
Alan P. Kozikowski, Ph.D., CEO and President, StarWise Therapeutics LLC
Alejandro Villagra, Ph.D., Assistant Professor, Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, The George Washington University
Wayne W. Hancock, M.D., Ph.D., Professor of Pathology and Chief of Transplant Immunology, Children’s Hospital of Philadelphia and University of Pennsylvania
Aimed at scientists working on or moving into the field of G protein-coupled receptors (GPCRs), this course will provide information on the identification and validation of allosteric, pathway-biased drugs including emerging screening approaches and practical tips and tools for ligand identification and validation. Allosteric modulators and pathway-biased ligands represent novel therapeutic approaches for achieving more selective actions with regards to GPCRs. The protein structural basis underlying the drug activity of allosteric modulators and the emerging opportunities for computer-aided discovery of allosteric and biased ligands will also be covered.
Annette Gilchrist, Ph.D., Professor, Pharmacology, Midwestern University
Sid Topiol, Ph.D., CSO, 3D-2drug, LLC; Professor and Director, Structural and Computational Drug Discovery, Stevens Institute of Technology
Phenotypic drug discovery is experiencing a Renaissance in the pharmaceutical industry, based on its successful track record in delivering first-in-class medicines. This approach offers the promise of delivering both novel targets and chemical matter modulating a disease phenotype of interest. Although phenotypic screening may appear at first sight to be similar to target-based screening, there are some significant differences between the two approaches. These need to be properly considered and addressed to ensure the greatest likelihood of success for phenotypic screening programs. This presentation will cover a range of relevant topics with a goal of providing practical information to help prosecute such programs more effectively.
Fabien Vincent, Ph.D., Associate Research Fellow, Hit Discovery and Lead Profiling Group, Pfizer
Covalent inhibitors of kinases have re-emerged as a drug design strategy due to more examples of their safety and efficacy in patients. Covalent inhibitors have the advantage of increased selectivity and longer action of duration but there are still important issues about their design and application that need to be better understood. This course will cover practical as well as theoretical issues that a medicinal chemist needs to keep in mind in developing covalent inhibitors.
Brian Gerstenberger, Ph.D., Principal Scientist, Medicinal Chemistry, Pfizer
Mark Schnute, Ph.D., Associate Research Fellow, Biotherapeutics Chemistry & Immunoscience Research, Pfizer Global R&D