Impact of agonist-directed stimulus on drug screening. Canonical strategies for high throughput (HTS) screening pass the most active molecules from the HTS (represented by the dextral tail of the Boltzman distribution representing the best responses in the HTS) into secondary assays and animal models for further testing. To detect bias in signaling, the active molecules from the HTS are all tested in another functional assay for another signaling pathway and the most active molecules from that assay pooled with the actives from the HTS for further testing. The most active molecules in the secondary biased assay often are not the most active in the HTS thus a spectrum of agonists of differing stimulus bias is tested in animal models.
Kenakin BMC Pharmacology and Toxicology 2012 13:3 doi:10.1186/2050-6511-13-3