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Related Experiment Video

Updated: May 13, 2026

A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules
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A Fluorescence-based Lymphocyte Assay Suitable for High-throughput Screening of Small Molecules

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An unbiased cell morphology-based screen for new, biologically active small molecules.

Masahiro Tanaka1, Raynard Bateman, Daniel Rauh

  • 1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, USA.

Plos Biology
|April 1, 2005
PubMed
Summary

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We discovered a new way to find small molecules that change cell shape, leading to the identification of carbonyl reductase 1 (CBR1) as a target. This finding offers new anticancer drug candidates and insights into cell death pathways.

Area of Science:

  • Chemical Biology
  • Cell Biology
  • Drug Discovery

Background:

  • Automated cell imaging and analysis systems enable unbiased screening of small molecules.
  • Morphological profiling can identify modulators of cellular processes and reveal unknown pathways.

Purpose of the Study:

  • To implement an unbiased cell morphology-based screen for identifying small-molecule modulators.
  • To discover novel targets and biological functions of small molecules using phenotypic screening.

Main Methods:

  • Utilized Cytometrix automated imaging and analysis for cell morphology screening.
  • Treated cancer cell lines with diverse small molecules and analyzed phenotypic readouts.
  • Employed multivariate statistical analysis and principal component analysis for compound classification.

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Last Updated: May 13, 2026

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  • Identified target of a novel compound (hydroxy-PP) using affinity purification and X-ray crystallography.

    • Main Results:

    • Identified carbonyl reductase 1 (CBR1) as a novel target of hydroxy-PP.
    • Determined the X-ray crystal structure of the CBR1/hydroxy-PP complex.
    • Developed potent and selective CBR1 inhibitors for biological studies.
    • Revealed a previously unknown role for CBR1 in serum-withdrawal-induced apoptosis.
    • Demonstrated that CBR1 inhibitors may enhance anthracycline anticancer efficacy.

    Conclusions:

    • Morphology-based screening is a powerful method for discovering small-molecule probes and anticancer drug candidates.
    • CBR1 plays a significant role in apoptosis and represents a potential therapeutic target.
    • Novel CBR1 inhibitors show promise for combination cancer therapy.