Hit-to-Lead (H2L)

The drug discovery phase between initial hit identification (from HTS, FBDD, or virtual screening) and lead optimization, focused on confirming activity, establishing SAR, and improving drug-like properties. Typically evaluates 100-500 compounds to narrow the field to 1-5 lead series. Key objectives include improving potency, selectivity, metabolic stability, and solubility while maintaining favorable ADME properties.

Exemples

• SAR exploration around an HTS kinase inhibitor hit
• Removing PAINS (pan-assay interference) compounds
• Counter-screening to confirm selectivity over related targets