Small Molecule Screening Strategies: Lead Identification and Validation
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Dr. Milka Kostic is the Program Director, Chemical Biology at Dana-Farber Cancer Institute. In this role, Dr. Kostic...
The genomics revolution has resulted in a vast amount of knowledge about human physiology and how different diseases affect function. Additional technological advancements, such as transcriptomics and proteomics have pushed insights even further. However, translating these findings into new drugs has progressed less rapidly. One of the bottlenecks is the challenge of going from the identity of the most appropriate cellular target, to having a drug, usually a small molecule, that affect the biology of the target in a manner that corrects the disease phenotype. A type of strategy developed to address this challenge is high-throughput screening (HTS). HTS is used to identify small molecules that bind a target of interest, leading to desired change in target’s behavior (usually activity) and/or to cellular phenotype of interest. These methods commonly use robotic sample handling, small volumes, rapid data acquisition, and sophisticated software and compound library management systems, to conduct thousands, even millions of small scale experiments and identify the most promising hit compounds. Moreover, high-throughput methods to validated the hits in terms of their binding affinities, selectivity, in-cell target engagement, pharmacokinetic and pharmacodynamic properties, reactivity, and stability are also on the rise. This methods collection captures some of the work in this area, and it is certain to grow further as new advancements in HTS methods continue to be reported. It is a resource for anyone interested in drug discovery and development, as well as hit identification and validation
1Virginia G. Piper Center for Personalized Diagnostics, Biodesign Institute, Arizona State University, 2Department of Pediatrics, and Biochemistry/Molecular Biology, College of Medicine, Pennsylvania State University
1Beijing Key Laboratory of Diagnostic and Traceability Technologies for Food Poisoning, Beijing Center for Disease Prevention and Control/Beijing Center of Preventive Medicine Research, China, 2College of Computer Science and Technology, Qilu University of Technology(Shandong Academy of Sciences), China, 3Key Laboratory of Computational Biology, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center for Genetics and Developmental Biology, Chinese Academy of Sciences-Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China, 4Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, China, 5School of Life Sciences, La Trobe University, Australia
1Chemical Biology Consortium Sweden, Science for Life Laboratory, Karolinska Institutet, Solna, 2Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, 3Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm
1Division of Cardiology, Department of Medicine, Zuckerberg San Francisco General and University of California San Francisco, 2Department of Cellular and Molecular Pharmacology and Howard Hughes Medical Institute, University of California San Francisco
1Department of Molecular and Biomedical Sciences, University of Maine, 2Graduate School of Biomedical Sciences and Engineering, University of Maine, 3School of Biology and Ecology, University of Maine, 4Division of Intramural Research, Immunity, Inflammation and Disease Laboratory, National Institute of Environmental Health Sciences, NIH, 5Department of Chemical and Biological Engineering, University of Maine
1Department of Molecular Medicine, The Scripps Research Institute, 2Department of Neuroscience, The Scripps Research Institute, 3Laboratory of Molecular Physiology, NHLBI, National Institutes of Health
1Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 2Singapore Immunology Network, A*STAR, 3Curiox Biosystems, 4Department of Immunobiology, Rega Institute for Medical Research, Katholieke Universiteit (KU) Leuven