Once a disease-associated target protein has been identified and verified, the process of compound screening is executed to ascertain the interaction between small molecules and the specific target protein. This interaction can involve activation or inhibition, aiming to pinpoint potential lead compounds for drug discovery.

To expedite lead discovery and enhance the pace of drug development, it is imperative to employ swift and effective screening technologies. High-throughput screening (HTS) capitalizes on automation and robotics to rapidly analyze extensive libraries of chemical compounds. This aids in identifying the most promising compounds worthy of pursuit as potential drug candidates. DNA-encoded library (DEL) screening involves attaching small molecule chemical compounds to short DNA fragments, allowing for simultaneous evaluation of a larger number of molecules to determine their activity and function. In the context of structure-based drug design screening, computational techniques are employed to predict the three-dimensional structures of compounds. These structures are then docked into binding sites, and the interaction between compounds and the target protein is assessed based on steric and electrostatic affinity. The most promising compounds identified through this process move on to subsequent biological testing.

The phase of hit-to-lead (H2L) research involves assessing hits, which are potential compounds identified in earlier screening stages. This evaluation includes analyzing their pharmacodynamic, physiochemical, and pharmacokinetic properties. The goal is to identify lead compounds that exhibit the desired characteristics for further optimization and in-depth analysis as potential candidates for drug development.