AI Article Synopsis
- - The study focuses on developing VEGFR-2 kinase inhibitors using an indazole structure, which is important for controlling tumor growth by blocking blood vessel formation.
- - The leading compound, 30, shows strong effectiveness in inhibiting VEGFR-2 with a low concentration needed (1.24 nM) and selectively targets it over other kinases.
- - In tests, compound 30 effectively limits blood vessel growth in cell models and shows low toxicity in mice, suggesting it has good potential for cancer treatment in future studies.
Article Abstract
The strategy of inhibiting angiogenesis, specifically by targeting vascular endothelial growth factor receptor 2 (VEGFR-2), has been proven effective in tumor treatment. In this study, we designed several VEGFR-2 kinase inhibitors based on an indazole scaffold. Among them, the most potent compound, 30, inhibits VEGFR-2 (IC = 1.24 nM) with subtle selectivity over other kinases. It demonstrates significant inhibitory activity against HUVEC angiogenesis and inhibits cell migration in a dose-dependent manner. Additionally, it exhibits low acute toxicity in mice. In vivo studies, compound 30 demonstrates favorable pharmacokinetic profiles. It suppresses tumor angiogenesis in the zebrafish subintestinal vessel model, indicating that it may be a potential angiogenesis inhibitor for further development.
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| http://dx.doi.org/10.1016/j.ejmech.2024.116889 | DOI Listing |
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