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Updated: Mar 9, 2026
A Simple Bioassay for the Evaluation of Vascular Endothelial Growth Factors
Published on: March 15, 2016
Discovery of novel dual VEGFR2 and Src inhibitors using a multistep virtual screening approach
Shangying Chen1, Chu Qin1, Jia En Sin1
1Department of Pharmacy, National University of Singapore, 18 Science Drive 4, Singapore 117543.
Aim:
Simultaneous inhibition of VEGFR2 and Src may enhance the efficacy of VEGFR2-targeted cancer therapeutics. Hence, development of dual inhibitors on VEGFR2 and Src can be a useful strategy for such treatments.
Materials & Methods:
A multistep virtual screening protocol, comprising ligand-based support vector machines method, drug-likeness rules filter and structure-based molecular docking, was developed and employed to identify dual inhibitors of VEGFR2 and Src from a large commercial chemical library. Kinase inhibitory assays and cell viability assays were then used for experimental validation.
Results:
A set of compounds belonging to six different molecular scaffolds was identified and sent for biological evaluation. Compound 3c belonging to the 2-amino-3-cyanopyridine scaffold exhibited good antiproliferative effect and dual-target activities against VEGFR2 and Src.
Conclusion:
This study demonstrated the ability of the multistep virtual screening approach to identify novel multitarget agents.
Insights
Developing dual inhibitors for Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) and Src kinase enhances cancer therapy. A virtual screening approach identified a novel compound with dual-target activity, showing promise for improved cancer treatment strategies.
Area of Science:
- Oncology
- Medicinal Chemistry
- Computational Drug Discovery
Background:
- VEGFR2 and Src kinases are crucial targets in cancer therapy.
- Simultaneous inhibition of VEGFR2 and Src may improve the efficacy of existing cancer treatments.
- Developing dual inhibitors offers a promising strategy for enhanced therapeutic outcomes.
Purpose of the Study:
- To identify novel dual inhibitors targeting both VEGFR2 and Src.
- To explore the potential of a multistep virtual screening protocol for discovering multitarget agents.
- To validate the efficacy of identified compounds through experimental assays.
Main Methods:
- A multistep virtual screening protocol was developed, integrating ligand-based support vector machines, drug-likeness filters, and structure-based molecular docking.
- A large commercial chemical library was screened to identify potential dual inhibitors.
- Kinase inhibitory and cell viability assays were performed for experimental validation.
Main Results:
- A set of compounds across six molecular scaffolds was identified.
- Compound 3c, from the 2-amino-3-cyanopyridine scaffold, demonstrated significant antiproliferative effects.
- Compound 3c exhibited dual-target inhibitory activity against both VEGFR2 and Src.
Conclusions:
- The multistep virtual screening approach is effective in identifying novel multitarget agents.
- Compound 3c represents a promising lead for developing dual VEGFR2 and Src inhibitors.
- This strategy holds potential for advancing VEGFR2-targeted cancer therapeutics.
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