Lead Optimization (Lead to Candidate)

In Lead Optimization, the project team strives to: Define desired levels of potency, efficacy, selectivity and pharmacokinetics;  Prepare analogs (variants) of the initial leads and assay for potency and selectivity, developing a structure-activity relationship (SAR) to catalyze the design of future analogs with enhanced properties;  Evaluate better analogs in animal disease models; Narrow down to candidate selection.  The small molecule, peptide and protein-based drug project teams perform similar activities in this stage, with respect to generating and evaluating variants of the lead but the actual goals, strategies and processes vary considerably.  Detailed discussion of these differences are beyond the scope of this website.  For starters the reader may wish to review the relevant chapters in the following books. 1, 2

  1. Bert Spilker, “Guide to Drug Development, A Comprehensive Review and Assessment”, Wolters Kluwer, Lippincott Williams & Wilkins, New York, 2009, p. 119-131
  2. Rick Ng, “Drugs, from Discovery to Approval”, 2nd Ed. 2009.