Bioactivity Signatures of Drugs Vs. Environmental Chemicals Revealed by Tox21 High-Throughput Screening Assays

Overview

Journal Front Big Data

Publisher Frontiers Media

Date 2021 Mar 11

PMID 33693373

Citations 6

Authors

Deborah K Ngan

Lin Ye

Leihong Wu

Menghang Xia

Anna Rossoshek

Anton Simeonov

Ruili Huang

Affiliations

Soon will be listed here.

Abstract

Humans are exposed to tens of thousands of chemicals over the course of a lifetime, yet there remains inadequate data on the potential harmful effects of these substances on human health. Using quantitative high-throughput screening (qHTS), we can test these compounds for potential toxicity in a more efficient and cost-effective way compared to traditional animal studies. Tox21 has developed a library of ~10,000 chemicals (Tox21 10K) comprising one-third approved and investigational drugs and two-thirds environmental chemicals. In this study, the Tox21 10K was screened in a qHTS format against a panel of 70 cell-based assays with 213 readouts covering a broad range of biological pathways. Activity profiles were compared with chemical structure to assess their ability to differentiate drugs from environmental chemicals, and structure was found to be a better predictor of which chemicals are likely to be drugs. Drugs and environmental chemicals were further analyzed for diversity in structure and biological response space and showed distinguishable, but not distinct, responses in the Tox21 assays. Inclusion of other targets and pathways to further diversify the biological response space covered by these assays is likely required to better evaluate the safety profile of drugs and environmental chemicals to prioritize for in-depth toxicological studies.

Citing Articles

Screening and characterization of 133 physiologically-relevant environmental chemicals for reproductive toxicity.

Ulaganathan G, Jiang H, Canio N, Oke A, Armstrong S, Abrahamsson D Reprod Toxicol. 2024; 126:108602.

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In vitro profiling of pesticides within the Tox21 10K compound library for bioactivity and potential toxicity.

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