Walters Lab Involved in Collaborative Research Investigating Reference Compounds for Characterizing Cellular Injury

March 17, 2023

High-throughput screening is a reliable method for discovering compounds that interact with novel therapeutic targets to improve human health. “Nuisance compounds” interfere with drug discovery by confounding screening results.

The Walters laboratory at the University of Minnesota (The Institute for Therapeutics Discovery and Development, and the Department of Medicinal Chemistry) collaborated with a broad group of researchers to develop methods to distinguish the pharmacological impact of such nuisance compounds in cellular assays. The method produced utilized the characterization of cellular injury using a technique referred to as cell painting. Cell painting allows the visualization and extraction of cell morphological features and their correlation with cellular phenotype. Cell phenotype fingerprints associated with a small set of informer compounds were characterized.

These fingerprints can now be used to identify, triage, or prioritize new compounds with unknown mechanisms of action. This finding can be used to decrease the negative impact on drug discovery of compounds that cause non-specific cell injury.

The group of international collaborators on this project hailed from the National Center for Advancing Translational Sciences (NCATS), the Broad Institute, Harvard Medical School, the National Cancer Institute (NCI), the Structural Genomics Consortium (Toronto, ON, Canada), the Department of Pharmaceutical Chemistry and Quantitative Biology Institute at the University of California, San Francisco (UCSF), The Department of Medical Biology, University of Melbourne, and the Medicinal Chemistry Theme, Monash University, Parkville, Australia.

Related Article:

Dahlin, J.L., Hua, B.K., Zucconi, B.E. et al. Reference compounds for characterizing cellular injury in high-content cellular morphology assays. Nat Commun 14, 1364 (2023).