Hit optimization

High-Throughput Screening and Hit Characterization

Depending on the accessibility of resources, a research project may begin with a high-throughput screening campaign, testing thousands to hundreds of thousands of small molecules against a specific target (1, 2). The nature of the assay—whether biochemical, phenotypic, or organelle-specific—can significantly affect the discovery rate, which may be as low as 0.1% (3, 4). This low rate means that actual active hit compounds are rare and highly valuable. Following validation through orthogonal assays, it is essential to thoroughly characterize each hit, focusing on the most critical parameters for the research objectives. This comprehensive analysis enables researchers to identify liabilities in the compound that require optimization, such as low cellular permeability, high lipophilicity, toxicity, and other factors (5).

Collaborative Opportunities

If you are interested in developing a collaborative project focused on hit optimization, please contact us.