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. 2024 Nov 25;4(12):4883-4891.
doi: 10.1021/jacsau.4c00851. eCollection 2024 Dec 23.

A Collection of Useful Nuisance Compounds (CONS) for Interrogation of Bioassay Integrity

Huabin Hu  1 , Xiangyan Yi  2 , Lian Xue  2 , Jonathan B Baell  2
Affiliations

A Collection of Useful Nuisance Compounds (CONS) for Interrogation of Bioassay Integrity

Huabin Hu et al. JACS Au. .

Abstract

High-throughput screening (HTS) is a crucial technique for identifying potential hits to fuel drug discovery pipelines. However, this process naturally concentrates nuisance compounds that are not optimizable yet signal positively in a convincing manner. To be able to understand what types of nuisance compounds a particular assay is sensitive to, would be of great utility in being able to prioritize progressable over nonprogressable screening hits. In this study, we present a carefully compiled set of over 100 nuisance compounds that are known to interfere with assay readouts in either phenotypic or target-based screenings. Readily accessible in an assay-ready screening plate, we believe this nuisance compound set will be of great interest to the research community, helping to establish high-quality HTS assays and identify promising, optimizable hits.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Representative colloidal aggregate-forming compounds. Displayed are common problematic compounds that disrupt assay readouts through colloidal aggregation mechanism, for which structural divergence is remarkable. The CAS number for each compound is provided along with its name in parentheses.
Figure 2
Figure 2
Metal ions and compounds that interfere with assay technologies (CIATs). Shown are three metal salts that mimic on-target activities and compounds that disrupt three widely used HTS assay technologies. The CAS number for each compound is provided along with its name in parentheses. Note the reappearance of quinone and THQ PAINS moieties.
Figure 3
Figure 3
Phenolic nuisance compounds. Displayed are characteristic phenolic phytochemicals that interfere with cell membranes. The CAS number for each compound is provided along with its name in parentheses.
Figure 4
Figure 4
Cationic amphiphilic drugs. Displayed are FDA-approved CADs with various clinical uses known to induce phospholipidosis with their hydrophilic amine headgroup that can be protonated in acidic conditions highlighted in red. The CAS number for each compound is provided along with its name in parentheses.
Figure 5
Figure 5
Representative pathway-associated/cellular poisons. Depicted are representative pathway-associated/cellular nuisance compounds. The CAS number for each compound is provided along with its name in parentheses.
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