HTS Follow-Up and Hit-to-Lead Initiation: Computational Approaches for Lead Identification

Our Eurofins Discovery scientists are industry leaders in High-throughput Screening (HTS). Their drug discovery experience is especially valuable at the completion of an HTS campaign, when a team must evaluate the hits and begin the lead identification process. At this stage, once hit compounds are validated in multiple experimental assays to confirm they are valid hits, and these hits become members of potential lead series.
 
Among the many areas where our Eurofins Discovery expertise stands out is in our analytics. We use computational approaches to rapidly explore these potential lead series by searching for chemical structures in or near in chemical space to these series to probe their activity against the therapeutic target, as well as evaluating the potential ADME and off-target liabilities which will need to be optimized during lead optimization.
 

 
Figure: A summary of the Eurofins virtual screening approach. A broad collection of databases can be searched from ideas from chemist to billion-compound make on demand collections. A variety of search probes can be used as well, including 2D chemical structures, 3D chemical structures, X-ray crystal structures, Cryo-EM structures or Alpha-Fold models can be used to search the large chemical collections. Once compounds pass the initial selection criteria, the remaining compounds are assessed using Eurofins AI-based ADME prediction tools to increase the likelihood that selected compounds will have good starting properties as they move forward in the drug discovery process.