In early drug discovery, the resulting leads from hit-to-lead high throughput screening (HTS) experiments undergo lead optimisation, to identify promising compounds. Potential leads are evaluated for a range of properties, including selectivity and binding mechanisms during lead optimisation, as the final step in early stage drug discovery. The purpose of lead optimisation is to maintain favourable properties in lead compounds, while improving on deficiencies in lead structure.
In order to produce a pre-clinical drug candidate, the chemical structures of lead compounds (small molecules or biologics) need to be altered to improve target specificity and selectivity. Pharmacodynamic and pharmacokinetic parameters and toxicological properties are also evaluated. Labs must acquire data on the toxicity, efficacy, stability and bioavailability of leads, in order to accurately characterise the compound and establish the route of optimisation.