Screening Strategies in Drug Discovery – Multimedia

High quality assays are required in order to take forward potential drugs, post screening. Therefore the liquid handling must be accurate and precise, as demonstrated in this experiment.

Epigenetic processes are attracting considerable attention in drug discovery as their fundamental roles in controlling normal cell development and contributions to disease states become more clearly defined. This work combines a fluorescence-based assay with liquid handling and dispensing instrumentation and a multi-mode reader which can be used to monitor the biological activity of the histone methyltransferase (HMT) G9a, a model system.

In this study, the Johns Hopkins Clinical Compound Library, containing approximately 1,500 FDA and foreign-approved clinical compounds, was used to screen a multi-drug resistant, triple negative breast cancer cell line for drug sensitivity.

The Acumen eX3 is the fastest imaging system available, collecting and simultaneously analysing over 40 images/second, covering the entire well, without the trade off of having to use lower resolution. Acumen is well established for cell-based high-content screening, but researchers have recently applied its large field of view to rapidly analyse complex cellular or animal models, such as angiogenic tube formation, C. elegans or drosophila larvae.

Residues 261-273 of type II collagen bound to the MHC class II allele HLA-DR4 play a crucial role in rheumatoid arthritis. The protein–protein interactions between TCR and CII-MHCII complex may therefore serve as targets for the development of new drugs against RA. The aim of this study is to develop a pharmacophore virtual screening followed by molecular docking and dynamics calculations leading to the identification of new TCR/CII-MHCII inhibitors.

This application note explains how to perform a rapid, high throughput screening assay of mutated photoprotein aequorin in order to find clones with more intense, slower kinetic, narrow spectral or color-shifted bioluminescent emission. Several examples of bioluminescent emission kinetics and spectra of mutated aequorins are included.

Early computational evaluation of drug candidate properties related to its pharmaceutical safety (such as hERG inhibition induced cardiotoxicity or CYP3A4 inhibition responsible various unwanted drug-drug interactions) is becoming increasingly important in the drug discovery process.

Two cell-based signaling assays from Invitrogen, Fluo-4 Direct™ Calcium Assay and Tango™-bla U2OS GPCR Assay, were performed on the PHERAstar FS HTS instrument. The PHERAstar FS has several unique features that enhance the performance of these assays including direct optic bottom reading, high resolution cell layer scanning, injection at the point of measurement and dual emission detection.

The Nucleofector® Technology enables efficient and reproducible transfection of primary cells and cell lines at throughputs of up to 96 samples per run. Nucleofection® now extends its range of application to deliver small molecules substrates and protein substrates such as peptides, proteins and antibodyconjugates.