Comment on Sjögren et al. (2018) A novel multi-parametric high-content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity in drug discovery. Arch Toxicol 92(10):3175–3190

2018 ◽  
Vol 93 (1) ◽  
pp. 221-223 ◽  
Author(s):  
Daniele Zink
Keyword(s):  
Drug Discovery ◽  
High Content Screening ◽  
Screening Assay ◽  
Drug Induced ◽  
Arch Toxicol

A novel multi-parametric high content screening assay in ciPTEC-OAT1 to predict drug-induced nephrotoxicity during drug discovery

2018 ◽  
Vol 92 (10) ◽  
pp. 3175-3190 ◽  
Author(s):  
Anna-Karin Sjögren ◽  
Katarina Breitholtz ◽  
Ernst Ahlberg ◽  
Lucas Milton ◽  
Malin Forsgard ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Content Screening ◽  
Screening Assay ◽  
Drug Induced

Development of a High-Content Screening Assay Panel to Accelerate Mechanism of Action Studies for Oncology Research

2012 ◽  
Vol 17 (8) ◽  
pp. 1005-1017 ◽  
Author(s):  
Danli L. Towne ◽  
Emily E. Nicholl ◽  
Kenneth M. Comess ◽  
Scott C. Galasinski ◽  
Philip J. Hajduk ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Mechanism Of Action ◽  
Large Scale ◽  
Morphological Changes ◽  
Single Cells ◽  
High Content Screening ◽  
Individual Compound ◽  
Screening Assay ◽  
Oncology Research ◽  
Protein Functions

Efficient elucidation of the biological mechanism of action of novel compounds remains a major bottleneck in the drug discovery process. To address this need in the area of oncology, we report the development of a multiparametric high-content screening assay panel at the level of single cells to dramatically accelerate understanding the mechanism of action of cell growth–inhibiting compounds on a large scale. Our approach is based on measuring 10 established end points associated with mitochondrial apoptosis, cell cycle disruption, DNA damage, and cellular morphological changes in the same experiment, across three multiparametric assays. The data from all of the measurements taken together are expected to help increase our current understanding of target protein functions, constrain the list of possible targets for compounds identified using phenotypic screens, and identify off-target effects. We have also developed novel data visualization and phenotypic classification approaches for detailed interpretation of individual compound effects and navigation of large collections of multiparametric cellular responses. We expect this general approach to be valuable for drug discovery across multiple therapeutic areas.

scholarly journals High-Content Screening: A New Approach to Easing Key Bottlenecks in the Drug Discovery Process

1997 ◽  
Vol 2 (4) ◽  
pp. 249-259 ◽  
Author(s):  
Kenneth A. Giuliano ◽  
Robbin L. DeBiasio ◽  
R. Terry Dunlay ◽  
Albert Gough ◽  
Joanne M. Volosky ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput Screening ◽  
Nuclear Dna ◽  
Spatial Information ◽  
Fluorescent Protein ◽  
Human Tumor ◽  
Nuclear Dna Content ◽  
High Content Screening ◽  
Drug Induced ◽  
Cell Functions

Recent improvements in target discovery and high throughput screening (HTS) have increased the pressure at key points along the drug discovery pipeline. High-content screening (HCS) was developed to ease bottlenecks that have formed at target validation and lead optimization points in the pipeline. HCS defines the role of targets in cell functions by combining fluorescence-based reagents with the ArrayScan™ System to automatically extract temporal and spatial information about target activities within cells. The ArrayScan System is a tabletop instrument that includes optics for subcellular resolution of fluorescence signals from many cells in a field within a well of a microtiter plate. One demonstrated application is a high-content screen designed to measure the drug-induced transport of a green fluorescent protein-human glucocorticoid receptor chimeric protein from the cytoplasm to the nucleus of human tumor cells. A high-content screen is also described for the multiparametric measurement of apoptosis. This single screen provides measurements of nuclear size and shape changes, nuclear DNA content, mitochondrial potential, and actin-cytoskeletal rearrangements during drug-induced programmed cell death. The next generation HCS system is a miniaturized screening platform, the CellChip™ System, that will increase the throughput of HCS, while integrating HCS with HTS on the same platform.

High-content screening of drug-induced cardiotoxicity using quantitative single cell imaging cytometry on microfluidic device

Lab on a Chip ◽  
2011 ◽  
Vol 11 (1) ◽  
pp. 104-114 ◽  
Author(s):  
Min Jung Kim ◽  
Su Chul Lee ◽  
Sukdeb Pal ◽  
Eunyoung Han ◽  
Joon Myong Song
Keyword(s):  
Single Cell ◽  
Microfluidic Device ◽  
Cell Imaging ◽  
High Content Screening ◽  
Drug Induced ◽  
Single Cell Imaging ◽  
Imaging Cytometry

A 96-well flow cytometric screening assay for detecting in vitro phospholipidosis-induction in the drug discovery phase

2009 ◽  
Vol 23 (2) ◽  
pp. 217-226 ◽  
Author(s):  
Mesens Natalie ◽  
Steemans Margino ◽  
Hansen Erik ◽  
Peters Annelieke ◽  
Verheyen Geert ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Screening Assay ◽  
Flow Cytometric ◽  
Discovery Phase

scholarly journals Development and pilot screen of novel high content assay for down regulators of expression of heterogenous nuclear ribonuclear protein H2

2020 ◽  
Author(s):  
Juan Diez ◽  
Sumitha Rajendrarao ◽  
Shadi A. Baajour ◽  
Praathibha Sripadhan ◽  
Timothy P. Spicer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
High Throughput Screening ◽  
Large Scale ◽  
Fluorescent Protein ◽  
High Content Screening ◽  
Screening Assay ◽  
Down Regulation ◽  
Metastatic Melanoma Cell ◽  
Heterogeneous Nuclear Ribonucleoprotein ◽  
Nuclear Ribonucleoprotein

ABSTRACTDespite recent advances in melanoma drug discovery, the average overall survival of patients with late stage metastatic melanoma is approximately 3 years, suggesting a need for new approaches and melanoma therapeutic targets. Previously we identified heterogeneous nuclear ribonucleoprotein H2 as a potential target of anti-melanoma compound 2155-14 (Palrasu et al, Cell Physiol Biochem 2019;53:656-86). In the present study, we endeavored to develop an assay to enable a high throughput screening campaign to identify drug-like molecules acting via down regulation of heterogeneous nuclear ribonucleoprotein H that can be used for melanoma therapy and research.ResultsWe established a cell-based platform using metastatic melanoma cell line WM266-4 expressing hnRNPH2 conjugated with green fluorescent protein to enable assay development and screening. High Content Screening assay was developed and validated in 384 well plate format, followed by miniaturization to 1,536 well plate format. All plate-based QC parameters were acceptable: %CV = 6.7±0.3, S/B = 21±2.1, Z’ = 0.75±0.04. Pilot screen of FDA-approved drug library (n=1,400 compounds) demonstrated hit rate of 0.5%. Two compounds demonstrated pharmacological response and were authenticated by western blot analysis.ConclusionsWe developed a highly robust HTS-amenable high content screening assay capable of monitoring down regulation of hnRNPH2. This assay is thus capable of identifying authentic down regulators of hnRNPH1 and 2 in a large compound collection and, therefore, is amenable to a large-scale screening effort.

scholarly journals EdU incorporation to assess cell proliferation and drug susceptibility for the brain-eating amoeba, Naegleria fowleri

2021 ◽  
Author(s):  
Emma V Troth ◽  
Dennis E Kyle
Keyword(s):  
Cell Proliferation ◽  
Drug Discovery ◽  
Quantitative Methods ◽  
Click Reaction ◽  
New Drugs ◽  
Alternative Methods ◽  
Naegleria Fowleri ◽  
Screening Assay ◽  
Nægleria Fowleri

Naegleria fowleri is a pathogenic free-living amoeba that is commonly found in warm, freshwater and can cause a rapidly fulminant disease known as primary amoebic meningoencephalitis (PAM). New drugs are urgently needed to treat PAM, as the fatality rate is >97%. Until recently, few advances have been made in the discovery of new drugs for N. fowleri and one drawback is the lack of validated tools and methods to enhance drug discovery and diagnostics research. In this study we aimed to validate alternative methods to assess cell proliferation that are commonly used for other cell types and develop a novel drug screening assay to evaluate drug efficacy on N. fowleri replication. EdU (5-ethynyl-2´-deoxyuridine) is a pyrimidine analog of thymidine that can be used as a quantitative endpoint for cell proliferation. EdU incorporation is detected via a copper catalyzed click reaction with an Alexa Fluor linked azide. EdU incorporation in replicating N. fowleri was validated using fluorescence microscopy and quantitative methods for assessing EdU incorporation were developed by using an imaging flow cytometer. Currently used PAM therapeutics inhibited N. fowleri replication and EdU incorporation in vitro. EdA (5'ethynyl-2'-deoxyadenosine), an adenine analog, also was incorporated by N. fowleri, but was more cytotoxic than EdU. In summary, EdU incorporation could be used as a complimentary method for drug discovery for these neglected pathogens.

scholarly journals High content screening for drug discovery from traditional Chinese medicine

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Wang ◽  
Ming-Yue Wu ◽  
Jie-Qiong Tan ◽  
Min Li ◽  
Jia-Hong Lu
Keyword(s):  
Drug Discovery ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
High Content Screening
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