Leads in the Drug Discovery Paradigm

The pharmaceutical industry is using the following (investigational) protocol for drug discovery [12]  

Secondary screening provides the experimental means to weed out HTS hits, and provide HTS actives or validated hits, that is, compounds with known structure and activity (at this stage, dose-response curves are standard). 

If multiple HTS actives of the same chemical family are to some extent leadlike (vide infra), they become a lead series, that is, structures that are amenable for further chemistry optimization and exhibit favorable patent situation [18, 19]. Lead series are further queried and derivatized in order to derive analogs with the appropriate blend of pharmacodynamic and pharmacokinetic properties. 

When all criteria are met, the optimized lead becomes a drug candidate. Typically, one in 100 000 HTS actives reaches this stage [20]. Following approval from regulatory authorities, drug candidates proceed to clinical trials. If all three phases of clinical trials prove successful, which only one in 10 candidate drugs [21] does, the compound is approved and becomes a launched (or marketed) drug. 

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