Biological mechanism profiling using an annotated compound library
Open accessAbstract
We present a method for testing many biological mechanisms in cellular assays using an annotated library of 2036 small organic molecules. This annotated compound library represents a large-scale collection of compounds with diverse, experimentally confirmed biological mechanisms and effects. We found that this chemical library is (1) more structurally diverse than conventional, commercially available libraries, (2) enriched in active compounds in a tumor cell viability assay, and (3) capable of generating hypotheses regarding biological mechanisms underlying cellular processes. We elucidated biological mechanisms relevant to the antiproliferative activity of 85 compounds from this library that were selected using a high-throughput cell viability screen. We developed a novel automated scoring system for identifying statistically enriched mechanisms among such a subset of compounds. This scoring system can identify both previously known and potentially novel antiproliferative mechanisms.
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Lipophilic antioxidants suppress erastin-induced death, implicating lipophilic reactive oxygen species in this process.
“Further studies [13, 17] identified lipophilic antioxidants (α-tocopherol, butylated hydroxytoluene and β-carotene) as strong suppressors of erastin-induced cell death, suggesting that reactive oxygen species (ROS), likely lipophilic in nature, were involved in this cell death process.”
From Ferroptosis: Death by Lipid Peroxidation (2016) · cites this paper as [17]
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References 52 · Cited by 95
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- Authors
- Root, D. E., Flaherty, S. P., Kelley, B. P., & Stockwell, B. R.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Stockwell, Brent R.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2003-09
- Volume
- 10
- Issue
- 9
- Pages
- 881-892
- ISSN
- 1074-5521 (ISSN-L)
- OpenAlex
- W2153019714
- Cited by
- 95
- References
- 52
- Citations by year
- 2025: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2018: 3 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 6
- FWCI
- 17.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3607 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (1R01CA97061-01, R01CA097061)
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- small organic molecules, antiproliferative activity, tumor cell viability, structural diversity, cell-based assays, hypothesis generation
- MeSH terms
- Cell Survival, Drug Screening Assays, Antitumor, Humans, Organic Chemicals, Proteins, Drug Delivery Systems, Combinatorial Chemistry Techniques, Cell Line, Tumor
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