Cited by 51Cell Image Analysis TechniquesComputational Drug Discovery MethodsAdvanced Proteomics Techniques and Applications

Compound Classification Using Image‐Based Cellular Phenotypes

Adams, Cynthia L., Kutsyy, Vadim, Coleman, Daniel A., Cong, Ge, Crompton, Anne Moon, Elias, Kathleen A., Oestreicher, Donald R., Trautman, Jay K. +1 more·2006·Methods in Enzymology

Abstract

Compounds with similar target specificities and modes of inhibition cause similar cellular phenotypes. Based on this observation, we hypothesized that we could quantitatively classify compounds with diverse mechanisms of action using cellular phenotypes and identify compounds with unintended cellular activities within a chemical series. We have developed Cytometrix technologies, a highly automated image-based system capable of quantifying, clustering, and classifying changes in cellular phenotypes for this purpose. Using this system, 45 out of 51 known compounds were accurately classified into 12 distinct mechanisms of action. We also demonstrate microtubule-binding activity in one of seven related cytochalasin actin poisons. This technology can be used for a variety of drug discovery applications, including high-throughput primary screening of chemical and siRNA libraries and as a secondary assay to detect unintended activities and toxicities.

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Crossref · 10.1016/s0076-6879(06)14024-0

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31 of 31 references verified0 citation errors · 0 not checkable

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Authors
Adams, C. L., Kutsyy, V., Coleman, D. A., Cong, G., Crompton, A. M., Elias, K. A., Oestreicher, D. R., Trautman, J. K., & Vaisberg, E.
Affiliations
Cytokinetics (United States) (US)
Venue
Methods in Enzymology
Publisher
Elsevier
Published
2006
Volume
414
Pages
440-468
ISSN
0076-6879 (ISSN-L)
OpenAlex
W1522234506
Cited by
51
References
35
Citations by year
2026: 1 · 2025: 3 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 1
FWCI
2.68
Type
book chapter
Language
en
Open access
closed
Locations
  • Methods in enzymology on CD-ROM/Methods in enzymology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
  • Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
compound classification, cell phenotype, mechanism of action, microtubule binding, cytochalasin, high-throughput screening, siRNA library
MeSH terms
Actins, Animals, Cells, Cultured, Cytochalasins, Cytological Techniques, Endothelium, Vascular, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Microscopy, Fluorescence, Phenotype, Combinatorial Chemistry Techniques, RNA, Small Interfering, Cell Line, Tumor, Cell Size

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