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Imaging Cell Membrane Injury and Subcellular Processes Involved in Repair

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Reference compounds for characterizing cellular injury in high-content cellular morphology assays.

Jayme L Dahlin^1,2, Bruce K Hua³, Beth E Zucconi⁴

¹National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, USA. jaymedahlin@gmail.com.

Nature Communications

|March 14, 2023

Summary

Identifying compounds with harmful mechanisms of action is crucial for drug development. This study profiles cytotoxic and nuisance compounds using cell painting, aiding in assay optimization and compound prioritization.

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Published on: September 22, 2019

Area of Science:

Chemical Biology
Toxicology
High-Throughput Screening

Background:

Identifying compounds with undesirable mechanisms of action in cellular assays is challenging.
This capability is vital for hit triage in high-throughput screening and predictive toxicology in drug development.

Purpose of the Study:

To generate cell painting and cellular health profiles for cytotoxic and nuisance compounds.
To establish a resource for improving assay optimization and compound prioritization in complex cellular assays.

Main Methods:

Profiling 218 cytotoxic and nuisance compounds in U-2 OS cells using cell painting and cellular health assays.
Utilizing a concentration-response format to capture detailed compound effects.

Main Results:

Diverse cytotoxic compounds, including cytoskeletal poisons, genotoxins, and electrophiles, exhibit distinct cell painting morphologies.
Distinguished lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles from selective compounds.
Demonstrated the utility of profiling reference cytotoxic and nuisance compounds.

Conclusions:

Cell painting profiles effectively capture the impact of various cytotoxic and nuisance compounds.
Profiling cytotoxic and nuisance compounds is essential for optimizing complex cellular assays like cell painting.
This resource aids in compound prioritization for drug discovery and toxicology.