Hit-to-Lead: Hit Validation and Assessment.

Area of Science:

• Drug discovery and development
• Biophysics
• Computational chemistry

Background:

• High-throughput screening (HTS) is crucial for identifying bioactive compounds.
• Hit validation and lead selection remain less standardized processes in drug discovery.

Purpose of the Study:

• To outline a comprehensive strategy for validating hits from HTS campaigns.
• To present diverse methods for assessing the quality of potential therapeutic compounds.

Main Methods:

• Chemical assessment of hit compounds.
• Application of computational approaches for hit evaluation.
• Utilization of counter-screens to confirm target specificity.
• Employing orthogonal biophysical assays such as NMR, SPR, ITC, and thermal shift assays.

Main Results:

• Demonstration of a multi-faceted approach to hit validation.
• Integration of chemical, computational, and biophysical data for robust hit assessment.
• Improved confidence in selecting high-quality hits for lead optimization.

Conclusions:

• A robust validation strategy is essential for successful drug discovery post-HTS.
• Combining diverse assay types enhances the reliability of hit validation.
• This framework aids in advancing promising compounds towards therapeutic development.