Drug Discovery → Lead Optimization

Lead Optimization

Lead optimization is the complex, non-linear process of refining the chemical structure of a confirmed hit to improve its drug characteristics with the goal of producing a pre-clinical drug
candidate. This stage frequently represents the bottleneck of a drug discovery program. Lead optimization employs a combination of empirical, combinatorial, and rational approaches. Criteria to confidently associate a candidate’s target and in vitro profile to its cellular or in vivo profile:

1. High potency: Demonstrates activity at low concentrations against the selected target. Typical in vitro potency is 1-100 nM
2. Selectivity: Preferentially acts on the target of interest relative to other protein targets
3. Activity in cellular, tissue or in vivo setting: 100 nM – 1 mM
4. Toxicity: Tolerated in animal models