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

Autor:	Ngan DK; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States., Ye L; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States., Wu L; National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, United States., Xia M; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States., Rossoshek A; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States., Simeonov A; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States., Huang R; Division of Pre-clinical Innovation, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH), Rockville, MD, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in big data [Front Big Data] 2019 Dec 13; Vol. 2, pp. 50. Date of Electronic Publication: 2019 Dec 13 (Print Publication: 2019).
DOI:	10.3389/fdata.2019.00050
Abstrakt:	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. (Copyright © 2019 Ngan, Ye, Wu, Xia, Rossoshek, Simeonov and Huang.)
Databáze:	MEDLINE
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