Welcome back to the drug discovery series! In this post, we journey through target validation and assay development and validation for compound screening!
As mentioned earlier in the series, most small molecule drugs function by modulating the activity of their particular target protein(s). Targets may be identified in a number of ways, for example, through studying disease pathophysiology to find disease-relevant pathways, or using genome and transcriptome analysis to identify proteins that are differentially expressed and/or aberrantly translated during disease. The early stages of any drug discovery effort must include extensive target validation, ideally through a broad combination of in vitro and in vivo (animal models), cellular and ‘omics’ approaches (1).
Compound Screening – Assay Design and Optimization
Compound screening is often carried out on a large scale, where millions of library compounds are screened. Screening on this scale is known as high throughput screening (HTS). If less than millions of compounds are deployed, one should consider low-to-medium throughput or collections of compounds. During screening, compounds are assayed for interactions with the target, typically in 96-, 384-, or 1536-well format. The nature of the interaction that is assayed between a compound and the target may be inhibition, activation, modulating, or binding.Continue Reading...