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About the Authors:
Haifeng Geng
Contributed equally to this work with: Haifeng Geng, Grace Whiteley
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Grace Whiteley
Contributed equally to this work with: Haifeng Geng, Grace Whiteley
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Jameson Ribbens
Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Wei Zheng
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Noel Southall
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Xin Hu
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Juan J. Marugan
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Marc Ferrer
Affiliation: National Institutes of Health, NIH Chemical Genomics Center, Rockville, Maryland, United States of America
Gustavo H. B. Maegawa
* E-mail: [email protected]
Affiliations McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America
Introduction
In the drug discovery process, the use of cell-based assays for high throughput screening (HTS) has become increasingly common as targets are presented in a more relevant biological context than classical in vitro biochemical assays [1]. Cell-based HTS assays also allow the identification of compounds that cross cell membranes, and reach specific cellular compartments, providing simultaneously cell permeability and cytotoxicity information at an earlier stage of the screening [2]. However, in most cellular HTS assays, cells utilized are usually not disease relevant. Thus, the use of patient-derived cell lines for HTS campaign brings considerable advantages when comparing with the traditional single target biochemical assays. Cellular assays using patient cells provide a unique opportunity to assess a target protein and/or pathway in the context of potentially disrupted biochemical and/or signaling pathways secondary to the disease process. In addition, this pathogenic in cellulo setting permits the evaluation of multiple intervention points, which are potentially altered in the disease, as opposed to commonly used cell-expression systems of a specific protein target...