Evaluating and evolving a screening library in academia: the St Jude approach

• Published in: Drug discovery today Vol. 26; no. 4; pp. 1060 - 1069
• Main Authors: Nishiguchi, Gisele, Das, Sourav, Ochoada, Jason, Long, Heather, Lee, Richard E., Rankovic, Zoran, Shelat, Anang A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2021
• Subjects: Drug Discovery - methods; Drug Discovery - organization & administration; High-Throughput Screening Assays - trends; Humans; Interdisciplinary Communication; Molecular Probes; Pharmaceutical Research - trends; Small Molecule Libraries - standards
• ISSN: 1359-6446; 1878-5832
• DOI: 10.1016/j.drudis.2021.01.005

•Analysis of our current library identified gaps and opportunities for enhancement.•We developed a 4-point strategy to build a screening library for the next decade.•We document our efforts to develop a lead-like library with high scaffold diversity.•Commercial libraries sample a small percentage of biologically relevant scaffolds.•Libraries should be tailored to meet the demands of academic vs. industrial settings. The quality of lead compounds is a key factor for determining the success of chemical probe and drug discovery programs. Given that high-throughput screening (HTS) continues to be a dominant lead generation paradigm, access to high-quality screening libraries is crucial for such efforts in both industry and academia. Here, we discuss the strategy implemented a decade ago to build from scratch one of the largest compound collections in academia, containing ∼575 000 carefully annotated small molecules, and a recent multidisciplinary effort designed to further enhance the collection to meet our research demands for the next decade.