The Drug Discovery Process: from Lead Optimization to the Clinical Candidate

The coordinated approaches characterizing a crucial stage of the drug discovery process, i.e., the optimization of lead compounds towards the selection of drug candidates for clinical phases, will be illustrated. The goal of this stage is to extensively optimize, in parallel, both the biological activity and the properties of the lead series, through a dedicated screening funnel of both in vitro and in vivo assays. The relevant steps of lead optimization, including medicinal chemistry, in vivo analysis, pharmacodynamics and toxicological assessment, solid state characterization and pre-formulation studies will be discussed together with a selection of meaningful case examples. The goal is to generate a lead clinical candidate and associated data package that strongly could support regulatory approval for the initiation of clinical target validation.