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A Strategy to Identify Compounds that Affect Cell Growth and Survival in Cultured Mammalian Cells at Low-to-Moderate Throughput

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Published on: September 22, 2019

Nuisance compounds in cellular assays.

Jayme L Dahlin¹, Douglas S Auld², Ina Rothenaigner³

¹National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD 20850, USA.

Cell Chemical Biology

|February 16, 2021

Summary

This summary is machine-generated.

Nuisance compounds in cellular assays can hinder drug discovery by causing assay interference. This review offers strategies to identify and manage these problematic compounds in cell-based screening.

Keywords:

artifacts chemical biology drug discovery high-content screening high-throughput screening interference nuisance compounds phenotypic drug discovery phenotypic screening

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Area of Science:

Chemical biology
Drug discovery
Cellular assay development

Background:

Nuisance compounds, exhibiting assay interference or undesirable bioactivity, are common in cellular assays like phenotypic and high-content screening.
While cell-free assay interference is well-understood, nuisance compounds in complex cell-based assays remain less characterized.
These compounds pose a significant obstacle to chemical biology and drug discovery by wasting resources and eroding scientific trust.

Purpose of the Study:

To summarize collective experiences with cellular nuisance compounds from academic, government, and industry settings.
To describe assay design strategies for mitigating the impact of nuisance compounds.
To suggest best practices for efficiently addressing nuisance compounds in complex biological settings.

Main Methods:

Review of academic, government, and industry experiences with nuisance compounds.
Analysis of assay design principles to counter nuisance compound effects.
Development of best practices for managing nuisance compounds in cell-based assays.

Main Results:

Nuisance compounds represent a major challenge in chemical biology and drug discovery.
Specific assay design strategies can mitigate the impact of these compounds.
Efficient methods for addressing nuisance compounds in complex biological systems are proposed.

Conclusions:

Addressing nuisance compounds is crucial for advancing chemical biology and drug discovery.
Proactive assay design and systematic management are key to overcoming challenges posed by nuisance compounds.
Implementing best practices will improve the reliability and efficiency of cell-based screening.