ArticleDrug design, development and therapy2014
Comparison of effects of anti-angiogenic agents in the zebrafish efficacy-toxicity model for translational anti-angiogenic drug discovery.
Article in Drug design, development and therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
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- Beyond the mouse: 3R-guided alternative animal models transforming cancer research.Molecular cancer · 2026Review
- Zebrafish Models of Arthritis and Their Applications in Traditional Chinese Medicine Screening: Advances and Perspectives.Journal of inflammation research · 2026Review
- VEGF signaling promotes blastema growth and proliferation of vascular and non-vascular cells during axolotl limb regeneration.Developmental biology · 2025Article
- Zebrafish as a Suitable Model for Utilizing the Bioactivity of Coumarins and Coumarin-Based Compounds.International journal of molecular sciences · 2025Review
- Toxicity assessment of imatinib mesylate and a related impurity: in vitro and in vivo approaches.Toxicology research · 2025Article
- Small Fish, Big Answers: Zebrafish and the Molecular Drivers of Metastasis.International journal of molecular sciences · 2025Review
- A dual readout embryonic zebrafish xenograft model of rhabdomyosarcoma to assess clinically relevant multi-receptor tyrosine kinase inhibitors.Frontiers in oncology · 2025Article
- The food dye Tartrazine disrupts vascular formation both in zebrafish larvae and in human primary endothelial cells.Scientific reports · 2024Article
- Identification of side effects of COVID-19 drug candidates on embryogenesis using an integrated zebrafish screening platform.Scientific reports · 2023Article
- Characterization and In Vivo Antiangiogenic Activity Evaluation of Morin-Based Cyclodextrin Inclusion Complexes.Pharmaceutics · 2023Article
- Flight for fish in drug discovery: a review of zebrafish-based screening of molecules.Biology letters · 2023Review
- Using a zebrafish xenograft tumor model to compare the efficacy and safety of VEGFR-TKIs.Journal of cancer research and clinical oncology · 2023Article
- Brain endothelial cells acquire blood-brain barrier properties in the absence of Vegf-dependent CNS angiogenesis.Developmental biology · 2023Article
- Automated in vivo compound screening with zebrafish and the discovery and validation of PD 81,723 as a novel angiogenesis inhibitor.Scientific reports · 2022Article
- Macrophages trigger cardiomyocyte proliferation by increasing epicardial vegfaa expression during larval zebrafish heart regeneration.Developmental cell · 2022Article
- The Inhibitory Effect of Selected DCells · 2022Article
- Article
- Anticancer Activity and In Vitro to In Vivo Mechanistic Recapitulation of Novel Ruthenium-Based Metallodrugs in the Zebrafish Model.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model.International journal of molecular sciences · 2021Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-angiogenic therapy in certain cancers has been associated with improved control of tumor growth and metastasis. Development of anti-angiogenic agents has, however, been saddled with higher attrition rate due to suboptimal efficacy, narrow therapeutic windows, or development of organ-specific toxicities. The aim of this study was to evaluate the translational ability of the zebrafish efficacy-toxicity model to stratify anti-angiogenic agents based on efficacy, therapeutic windows, and off-target effects to streamline the compound selection process in anti-angiogenic discovery.
methodsThe embryonic model of zebrafish was employed for studying angiogenesis and toxicity. The zebrafish were treated with anti-angiogenic compounds to evaluate their effects on angiogenesis and zebrafish-toxicity parameters. Angiogenesis was measured by scoring the development of subintestinal vessels. Toxicity was evaluated by calculating the median lethal concentration, the lowest observed effect concentration, and gross morphological changes. Results of efficacy and toxicity were used to predict the therapeutic window.
resultsIn alignment with the clinical outcomes, the zebrafish assays demonstrated that vascular endothelial growth factor receptor (VEGFR) inhibitors are the most potent anti-angiogenic agents, followed by multikinase inhibitors and inhibitors of endothelial cell proliferation. The toxicity assays reported cardiac phenotype in zebrafish treated with VEGFR inhibitors and multikinase inhibitors with VEGFR activity suggestive of cardiotoxic potential of these compounds. Several other pathological features were reported for multikinase inhibitors suggestive of off-target effects. The predicted therapeutic window was translational with the clinical trial outcomes of the anti-angiogenic agents. The zebrafish efficacy-toxicity approach could stratify anti-angiogenic agents based on the mechanism of action and delineate chemical structure-driven biological activity of anti-angiogenic compounds.
conclusionThe zebrafish efficacy-toxicity approach can be used as a predictive model for translational anti-angiogenic drug discovery to streamline compound selection, resulting in safer and efficacious anti-angiogenic agents entering the clinics.
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