High Throughput Screening (HTS) leverages automation, chemistry, biology and information technologies to rapidly assay the pharmacologic activity of drug-like molecules. As applied to drug discovery, it has been successful for discovering the precursors of marketed drugs as well as probes of various cellular and biochemical pathways. Scripps Florida is the home of the ?ultra? HTS (uHTS) Implementation core of the Scripps Research Institute Molecular Screening Center (SRIMSC). Core staff are responsible for developing and implementing the SRIMSC?s screening assays, managing the Molecular Libraries Small Molecule Repository (MLSMR) screening collection of >360,000 samples, screening the MLSMR library at a throughput in excess of 1 million samples per day, quality control &reporting of all screening results to the NIH?s publically available database (PubChem), cheminformatics support and overall project management for the SRIMSC. The core sustains full production capabilities for the NIH by screening the entire MLSMR compound library against more than 25 unique targets per year. As of this writing core staff have completed more than 185 high throughput screening campaigns for 175 molecular targets, with more than 40 million wells tested. Staff also execute lower-throughput bioassays to support the SRIMSC?s hit-to-probe medicinal chemistry efforts, participating in more than 50 probe development projects per year. Target classes screened by the core include receptors, transcription factors, transferases, hydrolases, oxidoreductases, lyases, isomerases and ligases;protein interactions (protein-protein, protein-DNA, and protein-RNA) and phenotypic bioassays. Targets have been purified for screening (e.g. enzymes or proteins) or assayed in whole-cell mammalian, bacterial, insect, yeast/fungal, and parasite systems. Screening formats include biochemical enzymatic &binding affinity assays, as well as whole-cell reporter gene, second messenger, membrane potential, ion flux, complementation, protein conformation, renaturation and toxicity assays. A variety of plate-based detection formats including kinetic (FLIPR, Alphascreen, TR-FRET, FP etc.) and high content analysis (HCA) are utilized for screening efforts. More information can be found at: http://hts.florida.scripps.edu/

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54MH084512-06
Application #
8525448
Study Section
Special Emphasis Panel (ZRG1-BCMB-D (50))
Program Officer
Brady, Linda S
Project Start
2008-09-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
6
Fiscal Year
2013
Total Cost
$7,866,000
Indirect Cost
$2,637,440
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Penas, Clara; Ramachandran, Vimal; Simanski, Scott et al. (2014) Casein kinase 1?-dependent Wee1 protein degradation. J Biol Chem 289:18893-903
Chang, Mi Ra; Lyda, Brent; Kamenecka, Theodore M et al. (2014) Pharmacologic repression of retinoic acid receptor-related orphan nuclear receptor ? is therapeutic in the collagen-induced arthritis experimental model. Arthritis Rheumatol 66:579-88
Yan, Fei; Yu, Yang; Chow, Dar-Chone et al. (2014) Identification of verrucarin a as a potent and selective steroid receptor coactivator-3 small molecule inhibitor. PLoS One 9:e95243
Sarkisyan, Gor; Gay, Laurie J; Nguyen, Nhan et al. (2014) Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth. Am J Physiol Cell Physiol 307:C14-24
Lewallen, Daniel M; Bicker, Kevin L; Madoux, Franck et al. (2014) A FluoPol-ABPP PAD2 high-throughput screen identifies the first calcium site inhibitor targeting the PADs. ACS Chem Biol 9:913-21
Lewallen, Daniel M; Sreelatha, Anju; Dharmarajan, Venkatasubramanian et al. (2014) Inhibiting AMPylation: a novel screen to identify the first small molecule inhibitors of protein AMPylation. ACS Chem Biol 9:433-42
Gentry, Patrick R; Kokubo, Masaya; Bridges, Thomas M et al. (2014) Development of a highly potent, novel M5 positive allosteric modulator (PAM) demonstrating CNS exposure: 1-((1H-indazol-5-yl)sulfoneyl)-N-ethyl-N-(2-(trifluoromethyl)benzyl)piperidine-4-carboxamide (ML380). J Med Chem 57:7804-10
Yun, Bogeon; Lee, HeeJung; Ghosh, Moumita et al. (2014) Serine hydrolase inhibitors block necrotic cell death by preventing calcium overload of the mitochondria and permeability transition pore formation. J Biol Chem 289:1491-504
Niphakis, Micah J; Cravatt, Benjamin F (2014) Enzyme inhibitor discovery by activity-based protein profiling. Annu Rev Biochem 83:341-77
Dreyton, Christina J; Anderson, Erin D; Subramanian, Venkataraman et al. (2014) Insights into the mechanism of streptonigrin-induced protein arginine deiminase inactivation. Bioorg Med Chem 22:1362-9

Showing the most recent 10 out of 80 publications