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Wednesday, June 16
7:30 am Continental Breakfast Break-Out Discussions
GPCRs and Ligand Bias
Moderator: Lisa K. Minor, Ph.D., President, In Vitro Strategies, LLC
Increasing the Relevancy of Cell Based Assays
Moderator: Charles Lunn, Ph.D., Research Fellow, New Lead Discovery, Merck Research Laboratories
To Kill, or Not to Kill a Program
In drug discovery, how to we manage targets with minimal biological validation?
How do progress target validation and make go/no go decisions based on chemical tractability and target validation?
Moderator: Elizabeth A. Davenport, Ph.D., Manager, Cell-Based Assay Development, Department of Biological Reagents and Assay Development, Glaxo Smith Kline
8:30 Chairperson's Remarks
Wei Zheng, Ph.D., Group Leader, NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health
8:40 Identification of Chemical Probes to Interrogate Complex Biology Using Integrated Biological Screening and Chemistry
Michelle Palmer, Ph.D., Director of Screening, Chemical Biology Platform, Broad Institute of Harvard and MIT
In addition to screening the large compound set used for MLPCN projects, we are also creating a novel library with stereochemical diversity and complexity similar to naturally occurring small molecules. These two separate collections are screened against many novel cell-based assays. Many of these assays utilize primary cells. The detection methods applied vary from phenotypic to target specific readouts. This presentation will discuss the screening strategies we have used to address a variety of biological questions and to improve our screening and probe development processes.
9:10 Utilization of Primary Cells for Phenotypic Screening in Hit Identification and Compound Profiling
Angela X. Dunne, B.Sc., M.Sc., Principal Scientist, GlaxoSmithKline
Primary cells have been used successfully at GSK to support HTS campaigns of more than 1 million compounds with subsequent compound profiling exceeding 500 compounds per week. Challenges of large scale production of purified primary cell samples originating from multiple donors are discussed, highlighting key assay development parameters that have been optimised to deliver high throughput, reliable and disease-relevant primary cell assays in miniaturised screening formats. Data demonstrates the identification of reproducibly active compounds, supporting the utilisation of primary cell assays in early phase drug discovery.
9:40 Application of Primary and Stem Cells as the Model System for Drug Screen
Wei Zheng, Ph.D., Group Leader, NIH Chemical Genomics Center, National Human Genome Research Institute, National Institutes of Health
In last two decades, engineered cell lines have been developed for studies of cell signaling pathways, transcription events, specific protein expressions and protein-protein interactions. Though many of these cell lines have been used in the cell-based assays for compound screens, cell-based assay for the disease model is still an unmet need. Recently, we have applied patient derived primary cells and stem cells as the model systems to screen the compound libraries and lead optimization. Our results suggest that the use of patient derived cells as the cell-based disease model systems may significantly accelerate drug discovery and development.
10:10 Networking Coffee Break, Poster and Exhibit Viewing
10:45 Chairperson’s Remarks
Larry A. Sklar, Ph.D., Distinguished Regents Professor of Pathology; Associate Director of Basic Research, University of New Mexico Cancer Center; Director, University of New Mexico Center for Molecular Discovery
10:50 Cell-Based Screening by High Throughput Flow Cytometry
Larry A. Sklar, Ph.D., Distinguished Regents Professor of Pathology; Associate Director of Basic Research, University of New Mexico Cancer Center; Director, University of New Mexico Center for Molecular Discovery
On behalf of the NIH Molecular Libraries Initiative (http://mli.nih.gov/mli/) and in collaboration with investigative teams worldwide, the University of New Mexico Center for Molecular Discovery (http://screening.health.unm.edu/) uses multiplexed high throughput flow cytometry for screening cellular and molecular targets such as receptors, transporters, signaling and adhesion pathways and phenotypic responses. Results are published at http://pubchem.ncbi.nlm.nih.gov/. Probe reports are published at https://mli.nih.gov/mli/mlp-probes/.
11:20 Polyplexed High Throughput Protein-Interaction Assays
Richard R. Neubig, M.D., Ph.D., Professor of Pharmacology; Associate Professor of Internal Medicine; Biophysics Research Division - Associated Faculty Medicinal Chemistry IDP; Center for Chemical Genomics, Associate Director, University of Michigan
We have developed a general approach - Flow Cytometry Protein Interation Assay (FCPIA) to assess protein-protein interactions in solution and lipid environments. Distinguishable bead sets combined with FCPIA permits the simultaneous quantitative analysis of the interaction of multiple members of a protein family with their target ligands. A high throughput screen using this Polyplexed FCPIA will be described
12:00 pm COLLABORATING WITH ACADEMIC SCREENING CENTERS
Moderator:
Michele Palmer, Ph.D., Director of Screening, Chemical Biology Platform, Broad Institute of Harvard and MIT
Panelists:
Peter Hodder, Ph.D., Senior Director, Lead Identification, Translational Research Institute, The Scripps Research Institute
Larry A. Sklar, Ph.D., Distinguished Regents Professor of Pathology; Associate Director of Basic Research, University of New Mexico Cancer Center; Director, University of New Mexico Center for Molecular Discovery
Chahrzad Montrose-Rafizadeh, Ph.D., Senior Research Advisor, Eli Lilly
Successful collaboration can be measured in many ways: movement of a compound forward in the pipeline, outsourcing to knowledge centers resulting in decreased project costs and the ability to focus on multiple targets without sacrificing timelines. Panel topics will include a basic review of what specialized opportunities are available at academic screening centers, including a brief description of the Molecular Libraries Probe Production Centers (MLPCN). In addition, a “success story” from the pharmaceutical industry will be presented that demonstrates either a positive movement forward of a candidate due to the screening performed or another similar example of success.
1:20 pm End of Conference
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