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Updated: Jul 9, 2026
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In Vivo Imaging and Quantitation of the Host Angiogenic Response in Zebrafish Tumor Xenografts
Published on: August 14, 2019
Automated, quantitative screening assay for antiangiogenic compounds using transgenic zebrafish
T Cameron Tran1, Blossom Sneed, Jamil Haider
1Zygogen, LLC, 24 Peachtree Center Avenue, 520 Kell Hall, Atlanta, GA 30303, USA.
Cancer Research
|December 7, 2007
Summary
Researchers developed a novel, automated zebrafish assay for identifying antiangiogenic compounds. This high-throughput screening method successfully identified known and a new compound, indirubin-3’-monoxime (IRO), with potent antiangiogenic activity in both zebrafish and human cells.
Area of Science:
- Pharmacology
- Developmental Biology
- Biotechnology
Background:
- Pathologic angiogenesis is a key therapeutic target in various diseases.
- Zebrafish embryos provide a vertebrate model for high-throughput drug discovery.
- Existing methods for identifying antiangiogenic compounds are often low-throughput.
Purpose of the Study:
- To develop and validate the first quantitative, automated assay for antiangiogenic compound identification using zebrafish embryos.
- To screen a compound library for novel antiangiogenic agents.
- To confirm the antiangiogenic activity of identified compounds in human cell-based assays.
Main Methods:
- Utilized transgenic zebrafish with fluorescent blood vessels for enhanced imaging.
- Developed automated methods for drugging and imaging zebrafish in 384-well plates.
- Created a custom algorithm for quantifying angiogenic blood vessels in zebrafish embryos.
- Screened the LOPAC1280 compound library.
Main Results:
- Identified two known antiangiogenic compounds (SU4312, AG1478) and one novel compound, indirubin-3'-monoxime (IRO).
- Demonstrated dose-dependent antiangiogenic activity for all identified compounds in zebrafish.
- Determined IC(50) values: SU4312 (1.8 µmol/L), AG1478 (8.5 µmol/L), and IRO (0.31 µmol/L), with IRO showing the highest potency.
- IRO inhibited human umbilical vein endothelial cell tube formation and proliferation (IC(50) 6.5 and 0.36 µmol/L, respectively).
Conclusions:
- The developed zebrafish assay is effective for high-throughput screening of antiangiogenic compounds.
- Indirubin-3'-monoxime (IRO) is a potent antiangiogenic compound discovered using this zebrafish assay and validated in human endothelial cells.
- This study establishes a new platform for discovering antiangiogenic therapeutics with potential for treating angiogenesis-related diseases.
