scholarly journals High-Throughput Screening of Small Molecule Libraries using SAMDI Mass Spectrometry

2011 ◽  
Vol 13 (4) ◽  
pp. 347-350 ◽  
Author(s):  
Zachary A. Gurard-Levin ◽  
Michael D. Scholle ◽  
Adam H. Eisenberg ◽  
Milan Mrksich
Keyword(s):  
Mass Spectrometry ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries

scholarly journals Sensitive ADAR editing reporter in cancer cells enables high-throughput screening of small molecule libraries

2018 ◽  
Vol 47 (4) ◽  
pp. e22-e22 ◽  
Author(s):  
Kajsa Fritzell ◽  
Li-Di Xu ◽  
Magdalena Otrocka ◽  
Claes Andréasson ◽  
Marie Öhman
Keyword(s):  
Cancer Cells ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries ◽  
Adar Editing

scholarly journals A Robust Multiplex Mass Spectrometric Assay for Screening Small-Molecule Inhibitors of CD73 with Diverse Inhibition Modalities

2018 ◽  
Vol 23 (3) ◽  
pp. 264-273 ◽  
Author(s):  
Jessica McManus ◽  
Timothy He ◽  
Julie-Ann Gavigan ◽  
Ghislaine Marchand ◽  
Stephanie Vougier ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Molecule ◽  
High Throughput Screening ◽  
Small Molecule Inhibitors ◽  
Dynamic Range ◽  
Elevated Concentration ◽  
Antitumor Effects ◽  
Extracellular Adenosine ◽  
Biochemical Assays ◽  
Small Molecule Libraries

CD73/Ecto-5′-nucleotidase is a membrane-tethered ecto-enzyme that works in tandem with CD39 to convert extracellular adenosine triphosphate (ATP) into adenosine. CD73 is highly expressed on various types of cancer cells and on infiltrating suppressive immune cells, leading to an elevated concentration of adenosine in the tumor microenvironment, which elicits a strong immunosuppressive effect. In preclinical studies, targeting CD73 with anti-CD73 antibody results in favorable antitumor effects. Despite initial studies using antibodies, inhibition of CD73 catalytic activity using small-molecule inhibitors may be more effective in lowering extracellular adenosine due to better tumor penetration and distribution. To screen small-molecule libraries, we explored multiple approaches, including colorimetric and fluorescent biochemical assays, and due to some limitations with these assays, we developed a mass spectrometry (MS)-based assay. Only the MS-based assay offers the sensitivity and dynamic range required for screening small-molecule libraries at a substrate concentration close to the Km value of substrate and for evaluating the mode of binding of screening hits. To achieve a throughput suitable for high-throughput screening (HTS), we developed a RapidFire–tandem mass spectrometry (RF-MS/MS)-based multiplex assay. This assay allowed a large diverse compound library to be screened at a speed of 1536 reactions per 40–50 min.

scholarly journals Discovery and Characterization of Orthosteric and Allosteric Muscarinic M2 Acetylcholine Receptor Ligands by Affinity Selection-Mass Spectrometry

2005 ◽  
Vol 11 (2) ◽  
pp. 194-207 ◽  
Author(s):  
Charles E. Whitehurst ◽  
Naim Nazef ◽  
D. Allen Annis ◽  
Yongmin Hou ◽  
Denise M. Murphy ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Acetylcholine Receptor ◽  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Size Exclusion ◽  
Affinity Selection ◽  
Binding Properties ◽  
Small Molecule Ligands

Screening assays using target-based affinity selection coupled with high-sensitivity detection technologies to identify small-molecule hits from chemical libraries can provide a useful discovery approach that complements traditional assay systems. Affinity selection-mass spectrometry (AS-MS) is one such methodology that holds promise for providing selective and sensitive high-throughput screening platforms. Although AS-MS screening platforms have been used to discover small-molecule ligands of proteins from many target families, they have not yet been used routinely to screen integral membrane proteins. The authors present a proof-of-concept study using size exclusion chromatography coupled to AS-MS to perform a primary screen for small-molecule ligands of the purified muscarinic M2 acetylcholine receptor, a G-protein-coupled receptor. AS-MS is used to characterize the binding mechanisms of 2 newly discovered ligands. NGD-3350 is a novel M2-specific orthosteric antagonist of M2 function. NGD-3366 is an allosteric ligand with binding properties similar to the allosteric antagonist W-84, which decreases the dissociation rate of N-methyl-scopolamine from the M2 receptor. Binding properties of the ligands discerned from AS-MS assays agree with those from in vitro biochemical assays. The authors conclude that when used with appropriate small-molecule libraries, AS-MS may provide a useful high-throughput assay system for the discovery and characterization of all classes of integral membrane protein ligands, including allosteric modulators.

scholarly journals Selecting, Acquiring, and Using Small Molecule Libraries for High‐Throughput Screening

2012 ◽  
Vol 4 (3) ◽  
pp. 177-191 ◽  
Author(s):  
Sivaraman Dandapani ◽  
Gerard Rosse ◽  
Noel Southall ◽  
Joseph M. Salvino ◽  
Craig J. Thomas
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries

Identification of Novel Quadruplex Ligands from Small Molecule Libraries by FRET-Based High-Throughput Screening

ChemBioChem ◽  
2011 ◽  
Vol 12 (9) ◽  
pp. 1422-1426 ◽  
Author(s):  
Armin Benz ◽  
Vijay Singh ◽  
Thomas U. Mayer ◽  
Jörg S. Hartig
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries

scholarly journals Yeast as a Model in High-Throughput Screening of Small-Molecule Libraries

2013 ◽  
pp. 455-482 ◽  
Author(s):  
Irene Stefanini ◽  
Carlotta De Filippo ◽  
Duccio Cavalieri
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries

scholarly journals Reporting data from high-throughput screening of small-molecule libraries

2007 ◽  
Vol 3 (8) ◽  
pp. 438-441 ◽  
Author(s):  
James Inglese ◽  
Caroline E Shamu ◽  
R Kiplin Guy
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries ◽  
Reporting Data

scholarly journals High throughput screening of small molecule libraries for modifiers of radiation responses

2011 ◽  
Vol 87 (8) ◽  
pp. 839-845 ◽  
Author(s):  
Kwanghee Kim ◽  
Robert Damoiseaux ◽  
Andrew J. Norris ◽  
Leena Rivina ◽  
Kenneth Bradley ◽  
...  
Keyword(s):  
Small Molecule ◽  
High Throughput ◽  
High Throughput Screening ◽  
Small Molecule Libraries
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