scholarly journals Repurposed high-throughput images enable biological activity prediction for drug discovery

2017 ◽  
Author(s):  
Jaak Simm ◽  
Günter Klambauer ◽  
Adam Arany ◽  
Marvin Steijaert ◽  
Jörg Kurt Wegner ◽  
...  
Keyword(s):  
Biological Activity ◽  
Drug Discovery ◽  
High Throughput ◽  
Chemical Structure ◽  
Cell Imaging ◽  
Protein Activity ◽  
Activity Prediction ◽  
Receptor Assay ◽  
Source Of Information ◽  
Structure Diversity

We repurpose a High-Throughput (cell) Imaging (HTI) screen of a glucocorticoid receptor assay to predict target protein activity in multiple other seemingly unrelated assays. In two ongoing drug discovery projects, our repurposing approach increased hit rates by 60- to 250-fold over that of the primary project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from available HTI screens are a rich source of information that can be reused to empower drug discovery efforts.

scholarly journals Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery

2018 ◽  
Vol 25 (5) ◽  
pp. 611-618.e3 ◽  
Author(s):  
Jaak Simm ◽  
Günter Klambauer ◽  
Adam Arany ◽  
Marvin Steijaert ◽  
Jörg Kurt Wegner ◽  
...  
Keyword(s):  
Biological Activity ◽  
Drug Discovery ◽  
High Throughput ◽  
Activity Prediction

scholarly journals High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

2009 ◽  
Vol 10 (1) ◽  
pp. 45 ◽  
Author(s):  
Serena Cervantes ◽  
Jacques Prudhomme ◽  
David Carter ◽  
Krishna G Gopi ◽  
Qian Li ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Antimalarial Drug ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Live Cell ◽  
Rna Probes

Quantitative analysis of aryl hydrocarbon receptor activation using fluorescence-based cell imaging—A high-throughput mechanism-based assay for drug discovery

Xenobiotica ◽  
2008 ◽  
Vol 38 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Helen Garside ◽  
Allison Stewart ◽  
Nick Brown ◽  
Emma-Louise Cooke ◽  
Mark Graham ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Drug Discovery ◽  
Aryl Hydrocarbon Receptor ◽  
High Throughput ◽  
Cell Imaging ◽  
Receptor Activation ◽  
Aryl Hydrocarbon

High-Throughput Drug Screening of ECM Deposition Inhibitors for Antifibrotic Drug Discovery

2019 ◽  
Author(s):  
Michael Gerckens ◽  
Hani Alsafadi ◽  
Darcy Wagner ◽  
Katharina Heinzelmann ◽  
Kenji Schorpp ◽  
...  
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
Drug Screening ◽  
High Throughput Drug Screening

Upscaling and Automation of Electrophysiology: Toward High Throughput Screening in Ion Channel Drug Discovery

2003 ◽  
Vol 9 (1) ◽  
pp. 49-58
Author(s):  
Margit Asmild ◽  
Nicholas Oswald ◽  
Karen M. Krzywkowski ◽  
Søren Friis ◽  
Rasmus B. Jacobsen ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Ion Channel ◽  
High Throughput ◽  
High Throughput Screening

The Role of Atelocollagen-Based Cell Transfection Array in High- Throughput Screening of Gene Functions and in Drug Discovery

2004 ◽  
Vol 1 (4) ◽  
pp. 287-294 ◽  
Author(s):  
Kimi Honma ◽  
Teruo Miyata ◽  
Takahiro Ochiya
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Cell Transfection ◽  
Gene Functions

scholarly journals A high-throughput screening assay based on automated microscopy for monitoring antibiotic susceptibility of Mycobacterium tuberculosis phenotypes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sadaf Kalsum ◽  
Blanka Andersson ◽  
Jyotirmoy Das ◽  
Thomas Schön ◽  
Maria Lerm
Keyword(s):  
Mycobacterium Tuberculosis ◽  
High Throughput ◽  
High Throughput Screening ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Imaging System ◽  
Aggregate Size ◽  
Live Cell ◽  
Screening Assay ◽  
High Throughput Screening Assay

Abstract Background Efficient high-throughput drug screening assays are necessary to enable the discovery of new anti-mycobacterial drugs. The purpose of our work was to develop and validate an assay based on live-cell imaging which can monitor the growth of two distinct phenotypes of Mycobacterium tuberculosis and to test their susceptibility to commonly used TB drugs. Results Both planktonic and cording phenotypes were successfully monitored as fluorescent objects using the live-cell imaging system IncuCyte S3, allowing collection of data describing distinct characteristics of aggregate size and growth. The quantification of changes in total area of aggregates was used to define IC50 and MIC values of selected TB drugs which revealed that the cording phenotype grew more rapidly and displayed a higher susceptibility to rifampicin. In checkerboard approach, testing pair-wise combinations of sub-inhibitory concentrations of drugs, rifampicin, linezolid and pretomanid demonstrated superior growth inhibition of cording phenotype. Conclusions Our results emphasize the efficiency of using automated live-cell imaging and its potential in high-throughput whole-cell screening to evaluate existing and search for novel antimycobacterial drugs.

High-Throughput Affinity Selection Mass Spectrometry Using SAMDI-MS to Identify Small-Molecule Binders of the Human Rhinovirus 3C Protease

2021 ◽  
pp. 247255522110232
Author(s):  
Michael D. Scholle ◽  
Doug McLaughlin ◽  
Zachary A. Gurard-Levin
Keyword(s):  
Mass Spectrometry ◽  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Human Rhinovirus ◽  
Binding Potential ◽  
Affinity Selection ◽  
Response Curves ◽  
Desorption Ionization ◽  
Self Assembled

Affinity selection mass spectrometry (ASMS) has emerged as a powerful high-throughput screening tool used in drug discovery to identify novel ligands against therapeutic targets. This report describes the first high-throughput screen using a novel self-assembled monolayer desorption ionization (SAMDI)–ASMS methodology to reveal ligands for the human rhinovirus 3C (HRV3C) protease. The approach combines self-assembled monolayers of alkanethiolates on gold with matrix-assisted laser desorption ionization time-of-flight (MALDI TOF) mass spectrometry (MS), a technique termed SAMDI-ASMS. The primary screen of more than 100,000 compounds in pools of 8 compounds per well was completed in less than 8 h, and informs on the binding potential and selectivity of each compound. Initial hits were confirmed in follow-up SAMDI-ASMS experiments in single-concentration and dose–response curves. The ligands identified by SAMDI-ASMS were further validated using differential scanning fluorimetry (DSF) and in functional protease assays against HRV3C and the related SARS-CoV-2 3CLpro enzyme. SAMDI-ASMS offers key benefits for drug discovery over traditional ASMS approaches, including the high-throughput workflow and readout, minimizing compound misbehavior by using smaller compound pools, and up to a 50-fold reduction in reagent consumption. The flexibility of this novel technology opens avenues for high-throughput ASMS assays of any target, thereby accelerating drug discovery for diverse diseases.

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