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Related Experiment Video

Updated: Jun 5, 2026

High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds
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High-Content Screening Assay for the Identification of Antibody-Dependent Cellular Cytotoxicity Modifying Compounds

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A high content screening assay for identifying lysosomotropic compounds.

Sashi Nadanaciva1, Shuyan Lu, David F Gebhard

  • 1Compound Safety Prediction, Worldwide Medicinal Chemistry, Pfizer Inc., Groton, CT 06340, USA. sashi.nadanaciva@pfizer.com

Toxicology in Vitro : an International Journal Published in Association with BIBRA
|December 28, 2010
PubMed
Summary

A new high-throughput screening assay identifies lysosomotropism, the accumulation of compounds in lysosomes, and cytotoxicity. This assay helps predict drug-induced toxicity by analyzing drug physicochemical properties.

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Area of Science:

  • Cell Biology
  • Pharmacology
  • Toxicology

Background:

  • Lysosomes are vital acidic organelles for cellular degradation and cell death.
  • Certain lipophilic compounds can accumulate in lysosomes, leading to dysfunction.
  • High-throughput screening methods are needed to detect lysosomotropism.

Purpose of the Study:

  • To develop and validate a high-content screening assay for measuring lysosomotropism and cytotoxicity.
  • To identify drugs that cause lysosomotropism using the developed assay.
  • To correlate physicochemical properties of drugs with their lysosomotropic potential.

Main Methods:

  • A 96-well, high-content screening assay utilizing quantitative image analysis.
  • Testing of forty diverse drugs (antidepressants, antipsychotics, antiarrhythmics, anticancer agents) in H9c2 cells.

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  • Analysis of drug physicochemical properties (ClogP and pKa) in relation to lysosomotropism.

    • Main Results:

    • The assay successfully identified known lysosomotropic drugs.
    • Gefitinib, lapatinib, and dasatinib were identified as novel lysosomotropic anticancer agents.
    • Lysosomotropic drugs shared physicochemical properties: ClogP > 2 and basic pKa between 6.5 and 11.

    Conclusions:

    • The developed assay is a robust and rapid tool for identifying lysosomotropic and cytotoxic compounds.
    • Lysosomotropism is linked to specific drug physicochemical properties.
    • This assay can aid in understanding drug-induced toxicity by evaluating lysosomotropism.