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Updated: May 19, 2026
A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos
Published on: November 8, 2014
A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish
Marco Radi1, Lasse Evensen, Elena Dreassi
1Dipartimento Farmaco Chimico Tecnologico, University of Siena,Via Alcide de Gasperi 2, I-53100 Siena, Italy.
Abstract:
A combined targeted/phenotypic approach for the rapid identification of novel antiangiogenics with in vivo efficacy is herein reported. Considering the important role played by the tyrosine kinase c-Src in the regulation of tumour angiogenesis, we submitted our in-house library of c-Src inhibitors to a sequential screening approach: in silico screening on VEGFR2, in vitro screening on HUVEC cells, ADME profiling, formulation and in vivo testing on a zebrafish model. A promising antiangiogenic candidate able to interfere with the vascular growth of a zebrafish model at low micromolar concentration was thus identified.
Insights
Researchers identified novel antiangiogenic compounds using a combined screening approach. A promising candidate effectively inhibited tumor angiogenesis in a zebrafish model at low concentrations.
Area of Science:
- Pharmacology and Drug Discovery
- Cancer Biology
- Angiogenesis Research
Background:
- Tumor angiogenesis is crucial for cancer growth and metastasis.
- Tyrosine kinase c-Src plays a significant role in regulating tumor angiogenesis.
- Targeting angiogenesis is a key strategy in cancer therapy.
Purpose of the Study:
- To develop a rapid, combined targeted and phenotypic approach for identifying novel antiangiogenic compounds.
- To screen a library of c-Src inhibitors for antiangiogenic activity.
- To evaluate the in vivo efficacy of identified candidates in a relevant model.
Main Methods:
- In silico screening of c-Src inhibitors against VEGFR2.
- In vitro screening using Human Umbilical Vein Endothelial (HUVEC) cells.
- Absorption, Distribution, Metabolism, and Excretion (ADME) profiling.
- Formulation development.
- In vivo efficacy testing in a zebrafish model.
Main Results:
- A sequential screening strategy successfully identified potential antiangiogenic agents.
- One promising candidate demonstrated efficacy in inhibiting vascular growth in a zebrafish model.
- The identified compound showed antiangiogenic activity at low micromolar concentrations.
Conclusions:
- A combined targeted/phenotypic screening approach is effective for rapid identification of novel antiangiogenics.
- c-Src inhibitors represent a viable class of compounds for antiangiogenic drug discovery.
- The identified candidate warrants further investigation for its therapeutic potential in cancer treatment.
