Discussion

Cell-based screening now accounts for about half of all HTS screens carried out in AstraZeneca. In most screens cell toxicity will lead to false positives. Toxicity is also a key reason for failure in the clinic and it is desirable to annotate clusters from HTS screens to alert projects as to which clusters may have a toxic liability.

Commonly the assays that have been run to assess compound toxicity have been cell viability assays using reagents such as Alamar Blue. There are many other assay reagents and methods that look at membrane integrity or a combination of readouts that give an assessment of apoptosis of the cells.

In this poster we will present data to allow comparison across 3 different methods, Alamar Blue (cell viability), Promega Celltox Green (membrane integrity) and a flow cytometry multiplex assay for apoptosis, for assessing cytotoxicity in THP-1 cells. We will exemplify this with a subset of compounds identified from a 400K well high throughput screen that was designed to annotate AstraZeneca’s compound collection to enable improved decision making following cell-based screening activities.