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Combinatorial Chemistry & High Throughput Screening
ISSN (Print): 1386-2073
ISSN (Online): 1875-5402
VOLUME: 17
ISSUE: 4
DOI: 10.2174/1386207317666140323132222









Chemical & RNAi Screening at MSKCC: A Collaborative Platform to Discover & Repurpose Drugs to Fight Disease

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Author(s): Bhavneet Bhinder, Christophe Antczak, David Shum, Constantin Radu, Jeni P. Mahida, Nancy Liu-Sullivan, Glorymar Ibanez, Balajee Somalinga Raja, Paul A. Calder and Hakim Djaballah
Pages 298-318 (21)
Abstract:
Memorial Sloan Kettering Cancer Center (MSKCC) has implemented the creation of a full service state-of-the-art High-throughput Screening Core Facility (HTSCF) equipped with modern robotics and custom-built screening data management resources to rapidly store and query chemical and RNAi screening data outputs. The mission of the facility is to provide oncology clinicians and researchers alike with access to cost-effective HTS solutions for both chemical and RNAi screening, with an ultimate goal of novel target identification and drug discovery. HTSCF was established in 2003 to support the institution’s commitment to growth in molecular pharmacology and in the realm of therapeutic agents to fight chronic diseases such as cancer. This endeavor required broad range of expertise in technology development to establish robust and innovative assays, large collections of diverse chemical and RNAi duplexes to probe specific cellular events, sophisticated compound and data handling capabilities, and a profound knowledge in assay development, hit validation, and characterization. Our goal has been to strive for constant innovation, and we strongly believe in shifting the paradigm from traditional drug discovery towards translational research now, making allowance for unmet clinical needs in patients. Our efforts towards repurposing FDA-approved drugs fructified when digoxin, identified through primary HTS, was administered in the clinic for treatment of stage Vb retinoblastoma. In summary, the overall aim of our facility is to identify novel chemical probes, to study cellular processes relevant to investigator’s research interest in chemical biology and functional genomics, and to be instrumental in accelerating the process of drug discovery in academia.
Keywords:
Automation, cell-based assay, chemical, drug discovery, HCS, HTS, miRNA, RNAi, robotics, screen data analysis, shRNA, siRNA, small molecule, target-based assay.
Affiliation:
HTS Core Facility, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.