Typically the initial screening hits display binding affinities for their biological target in the micromolar (10−6 molar concentration) range.
Through limited H2L optimization, the affinities of the hits are often improved by several orders of magnitude to the nanomolar (10−9 M) range.
The next step will allow the testing of analogous compounds to determine a quantitative structure-activity relationship (QSAR).
The objective of this drug discovery phase is to synthesize lead compounds, new analogs with improved potency, reduced off-target activities, and physiochemical/metabolic properties suggestive of reasonable in vivo pharmacokinetics.
For educational purposes the European Federation for Medicinal Chemistry and Chemical Biology (EFMC) shared a series of webinars including 'Best Practices for Hit Finding' as well as 'Hit Generation Case Studies'.