Once a target protein implicated in a disease has been identified and validated, compound screening is performed to determine how small molecules interact with that specific target protein, by either activating or inhibiting it, for lead identification in drug discovery.
To accelerate lead discovery, and thereby the rate of drug discovery, rapid and efficient screening technologies are essential. High-throughput screening (HTS) leverages automation and robotics for the quick analysis of large chemical compound libraries to ultimately detect compounds most suitable to pursue as drug candidates. DNA-encoded library (DEL) screening allows for mass conjugation of small molecule chemical compounds to short DNA fragments, so that a greater number of molecules can be examined for the desired activity and function simultaneously. In structure-based drug design screening, 3D structures of compounds are predicted using in silico techniques where entire libraries are docked into binding sites and the steric and electrostatic affinity between the compounds and target protein are evaluated. The highest ranked compounds then progress to biological testing.
Hit-to-lead (H2L) research evaluates the pharmacodynamic, physiochemical, and pharmacokinetic properties of hits to identify lead compounds for lead optimization and further analysis as potential candidates for drug development.