(1392-A) Using DNA Encoded Library Selections and Hit Calling to Predict Target Tractability and Accelerate Portfolio Activities.
Monday, February 5, 2024
12:00 PM – 1:00 PM EST
Location: Exhibit Halls AB
Abstract: Recent advances in genome-wide screening and genome-wide analyses have enabled the identification of numerous putative therapeutically relevant protein targets for hit identification programs. These targets often represent under studied and historically difficult protein classes to target with small molecules. Pursuing all these targets in small molecule hit ID programs is not feasible but is critical to better understand these often-overlooked potential therapeutic proteins. Encoded Library Technology (ELT) is a hit identification platform that uses large collections of chemically diverse DNA-encoded small molecules that are selected for against therapeutically relevant targets. Though exposure to such high chemical diversity provides a better chance of identifying small molecule binders with lead-like properties, it also consumes high amounts of DNA-encoded small molecules and requires greater sequencing depth and data analysis efforts. These factors often result in extended decision-making timelines. At GSK, we have integrated both in silico and experimental methods to rapidly predict the small molecule tractability of novel targets. Using novel library pooling methods and post selection hit calling/ QC metrics, we can rapidly predict tractability for dozens of potential drug targets simultaneously. We have shown that these initial tractability efforts are able to successfully predict the success rates of projects in the portfolio. These tools allow us to quickly prioritize novel therapeutically relevant targets based on empirical data and focus small molecule hit identification efforts on those that are most likely to succeed and have the greatest therapeutic impact for patients.