PUBLICATION
A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation
- Authors
- Radi, M., Evensen, L., Dreassi, E., Zamperini, C., Caporicci, M.L., Falchi, F., Musumeci, F., Schenone, S., Lorens, J.B., and Botta, M.
- ID
- ZDB-PUB-120807-28
- Date
- 2012
- Source
- Bioorganic & medicinal chemistry letters 22(17): 5579-5583 (Journal)
- Registered Authors
- Evensen, Lasse, Lorens, James B.
- Keywords
- angiogenesis, kinase, zebrafish, ADME
- MeSH Terms
-
- Angiogenesis Inhibitors/chemistry*
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Cyclodextrins/chemistry
- Drug Carriers/chemistry
- Drug Discovery/methods*
- Embryo, Nonmammalian/blood supply*
- Embryo, Nonmammalian/drug effects
- Human Umbilical Vein Endothelial Cells
- Humans
- Models, Animal
- Neovascularization, Pathologic/drug therapy*
- Neovascularization, Physiologic/drug effects*
- Proto-Oncogene Proteins pp60(c-src)/antagonists & inhibitors
- Proto-Oncogene Proteins pp60(c-src)/metabolism
- Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors
- Vascular Endothelial Growth Factor Receptor-2/metabolism
- Zebrafish/embryology
- PubMed
- 22853993 Full text @ Bioorg. Med. Chem. Lett.
Citation
Radi, M., Evensen, L., Dreassi, E., Zamperini, C., Caporicci, M.L., Falchi, F., Musumeci, F., Schenone, S., Lorens, J.B., and Botta, M. (2012) A combined targeted/phenotypic approach for the identification of new antiangiogenics agents active on a zebrafish model: From in silico screening to cyclodextrin formulation. Bioorganic & medicinal chemistry letters. 22(17):5579-5583.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping