SC10: Introduction to Allosteric Modulators and Biased Ligands of GPCRs

WEDNESDAY, SEPTEMBER 27, 2017 | 7:00 - 9:30 pm

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.

  • Overview of allosteric modulators and pathway biased ligands
  • Approaches for screening and validation
  • Insights into GPCR structural “pressure points”
  • Structure-based options for docking and design of allosteric and biased ligands

Instructors:

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


Annette_GilchristAnnette Gilchrist, Ph.D., Professor, Pharmacology, Midwestern University

Dr. Gilchrist works on allosteric and/or biased modulators for a number of different GPCRs including PAR1, CCR1, and FFAR2. She also serves as the Senior Online Editor for British Journal of Pharmacology and British Journal of Clinical Pharmacology. In addition to editing the book “GPCR Molecular Pharmacology and Drug Targeting: Shifting Paradigms and New Directions” published by John Wiley and Sons she has written chapters on G protein signaling and CCR1 antagonists.

Currently she is working with Dr. Paula Stern as a guest editor for Frontiers in Endocrinology for a themed issue on “Chemokines and Bone”. Previously, she was with Cue Biotech and Caden Biosciences, companies she co-founded that focused on GPCRs and used a novel approach to identify allosteric compounds based on their ability to modulate GPCR/G protein coupling (US Patent Numbers 7,208,279 and 7,294,472). Prior to that Dr. Gilchrist worked as an Assistant Research Professor in the Department of Molecular Pharmacology & Biological Chemistry at Northwestern University where she developed a set of unique tools known as minigene vectors (US Patent Number 6,559,128). Minigene vectors allow one to dissect out the G protein that mediates a given physiological function and they have been widely adopted by researchers around the world. Preceding that Dr. Gilchrist was a postdoctoral fellow with Dr. Heidi Hamm. In this setting, she identified high affinity peptides that mimic the C-terminus of Ga, and were later used for crystallization of rhodopsin. Dr. Gilchrist’s work on GPCRs began with her graduate studies in which she studied signaling of chemokine receptors through tyrosine kinases and phosphatases. Dr. Gilchrist has a PhD in Immunology from the University of Connecticut Health Center and a MS in Biochemistry from the University of Connecticut.

Sid_TopiolSid Topiol, Ph.D., CSO, 3D-2drug, LLC; Professor and Director, Structural and Computational Drug Discovery, Stevens Institute of Technology

Sid Topiol received his B.S. from CCNY and his Ph.D. from NYU. He trained as a theoretical quantum chemist. He post-docked at Northwestern with Mark Ratner and Arthur Frost, and at Carnegie-Mellon with John Pople (Noble laureate.) He first joined The Mount Sinai School of Medicine in the Department of Pharmacology. He has spent over 20 years in Pharma, starting with Berlex followed by Sandoz/Novartis and then Lundbeck. He has worked on all aspects of Structural and Computer Aided Drug Discovery in interdisciplinary project environments. He now engages in industrial and academic activities. In 2010 he formed 3D-2Drug, a consulting company which provides the means for the most efficient drug discovery activities through advanced scientific approaches. In 2011 he began teaching as an Adjunct Lecturer at New Jersey Institute of Technology and has, in 2014, joined the newly forming Center for Healthcare Innovation at the Stevens Institute of Technology.