This two-day virtual workshop hosted by NCATS Assay Guidance Manual (AGM) covered a broad range of critical concepts underlying assay development and implementation for high-throughput screening and lead discovery projects. The videos from the first day of the workshop are below.
Welcome to the AGM Workshop
Christopher P. Austin, M.D.
Director
National Center for Advancing Translational Sciences (NCATS)
In his welcome address, Dr. Austin introduces the audience to NCATS, its mission to conduct and disseminate translational science, and to the Assay Guidance Manual (AGM). Dr. Austin also highlights the upcoming events on the AGM calendar.
Robust or Go Bust: An Introduction to the Assay Guidance Manual
Sarine Markossian, Ph.D.
Editor-in-Chief, Assay Guidance Manual (AGM); Lead, AGM Translational Science Resources Program
National Center for Advancing Translational Sciences (NCATS)
Dr. Markossian introduces the audience to assays and their importance in the drug discovery pipeline, and to the Assay Guidance Manual (AGM) program including the e-book and the workshops. Dr. Markossian also highlights the objectives and goals of the workshop.
Target Qualification Strategies: Functional Genomics for Target ID and Validation
Yueming Wang Ph.D.
Principal Scientist, Primary Pharmacology Group, Medicine Design
Pfizer Inc.
Dr. Wang discusses the importance of improving the quality of target selection and details strategies to achieve that goal. He also takes a deep dive into the importance of functional genomics for target ID and validation.
Strategies for Assay Selection and for the Development of Robust Biochemical Assays
Nathan P. Coussens, Ph.D.
Director, Molecular Pharmacology Laboratories
Frederick National Laboratory for Cancer Research
Dr. Coussens discusses strategies for choosing the right assay for HTS. Dr. Coussens also expands on biochemical assays for enzymes and for molecular interactions.
Treating Cells as Reagents to Design Reproducible Assays
Terry Riss, Ph.D.
Senior Product Manager, Cell Health
Promega Corporation
Dr. Riss provides strategies to help design reproducible cell-based assays. He also addresses the major causes of variability in cell-based assays and provides avenues for establishing SOPs for consistent handling of cells.
High Content Imaging Applications: Best Practices and Approaches to Consider
Joe Trask
Product Line Leader & Senior Application Scientist, Cellular Imaging and Analysis
PerkinElmer
Mr. Trask introduces the audience to all of the current and upcoming AGM high-content screening (HCS) chapters. This talk also covers an overview of a typical HCS Workflow including its bottlenecks, 3D HCS imaging considerations and an introduction to cell painting.
Biophysical Approaches to Small Molecule Discovery and Validation
Michelle Arkin, Ph.D.
Professor, Pharmaceutical Chemistry; Co-Director, Small Molecule Discovery Center
University of California, San Francisco
Dr. Arkin describes the role of biophysical methods in drug discovery. Dr. Arkin first provides an overview of commonly used methodologies, and then describes fragment-based discovery as an application of biophysical methods in screening.
Compound-mediated Interferences in Homogeneous Proximity Assays
Jayme L. Dahlin, M.D., Ph.D., FASCP
Preclinical Medical Director, A Specialized Platform for Innovative Research Exploration (ASPIRE)
National Center for Advancing Translational Sciences (NCATS)
Dr. Dahlin provides a background on homogeneous proximity assays and discusses several compound interference mechanisms in these assays. Dr. Dahlin also provides strategies to identify and mitigate compound interferences.
In Vitro Toxicological Testing using a qHTS Platform
Menghang Xia, Ph.D.
Group leader, Systems Toxicology, Division of Preclinical Innovation
National Center for Advancing Translational Sciences (NCATS)
Dr. Xia introduces the audience to the Tox21 program and further discusses the selection and design of assays used in this program. She then presents a case study for a mitochondrial membrane potential assay as an example of an application of qHTS in toxicology.
Lead Selection and Optimization by Medicinal Chemistry
Samarjit Patnaik, Ph.D.
Group Leader, Chemistry, Early Translation Branch, Division of Preclinical Innovation
National Center for Advancing Translational Sciences (NCATS)
Dr. Patnaik emphasizes the importance of assay development to medicinal chemistry. He discusses multiple case studies where a change in the assay platform or conditions led to the discovery of unexpected activities of compounds.
In Vitro Assessment of ADME Properties of Lead Compounds
Xin Xu, Ph.D.
Senior scientist and the director of pharmacokinetics (PK), Therapeutics Development Branch, Division of Preclinical Innovation
National Center for Advancing Translational Sciences (NCATS)
Dr. Xu describes the importance of ADME/PK concepts in drug discovery and development. She also describes the development of in vitro assays to address key ADME issues, and introduces common ADME assays used in drug discovery and development.