Screening Strategies in Drug Discovery – Multimedia

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.

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.

Capillary electrophoresis, which was pioneered for HTS in the 1990s, has recently been adapted to enable the screening of fragments. The technique is explained and the screening of fragments against a chaperone protein Hsp90 is presented as an example.

We report synthesis and biological evaluation of novel thiazole derivatives. High throughput screening of various compounds for their anti-proliferative activity led to the identification of thiazolo-thiones as potential candidate for Lung cancer (NCl-H23, NClH510A, NCI-H522) and breast cancer (MDA-MB-453/231/468, MCF-7). The most potent compounds were also screened for their inhibitory activity against CDK2/ Cyclin E/A which are considered as promising targets for lung and breast cancer.

ATP depletion assays of kinases, ATPases and aminoacyl tRNA synthetases can be performed in the presence of firefly luciferase/luciferin, by monitoring the light emission continuously. Such assays are preferably set up to result in a first order reaction rate with respect to ATP consumption.

The use of cellular assays in drug screening continues to grow with over 50% of primary screens using cell based formats in 2006. The majority of cells used in the drug discovery industry are fresh, using ‘just in time’ batch processing from in house facilities. This process could give rise to a number of issues, namely batch variation, scheduling of cell production and capacity management. We describe the use of microcarrier technology in combination with a suitably configured bioreactor to pro

The recent growth in cell use for drug discovery, particularly for high-throughput screening (HTS), has posed a number of challenges including batch performance, cell production scheduling and capacity management in response to the increasing demands for cells and assay components derived from cells (e.g. membrane fractions).

The use of mammalian cell based assays in compound screening continues to grow. Over 50% of all screening assays (HTS and HCA) now utilise cells or cell derived reagents.

High Throughput Screening (HTS) labs are required to screen ever-increasing numbers of compounds against an increasing number and variety of assay types. With a level of flexibility and adaptability unsurpassed in the world of automated systems, HighRes’ MicroStar™ is ideal. It meets not only today’s lab requirements; it also anticipates the easy exchange of today’s components with tomorrow’s technology.

Measurement of the mitochondrial membrane potential is useful in a variety of research areas. Mitochondrial membrane potential is usually measured using non-invasive cationic dyes. These dyes are sequestered into the mitochondrial matrix in amounts directly proportional to the membrane potential. BMG LABTECH’s FLUOstar Omega was used in an hts assay measuring mitochondrial membrane potential in human cells. The results presented here were gained using primary human fibroblast cells from controls