Discovery of a New Series of Naphthamides as Potent VEGFR‑2 Kinase Inhibitors

Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibit...

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Published in:ACS medicinal chemistry letters 2014-05, Vol.5 (5), p.592-597
Main Authors: Lv, Yongcong, Li, Mengyuan, Liu, Ting, Tong, Linjiang, Peng, Ting, Wei, Lixin, Ding, Jian, Xie, Hua, Duan, Wenhu
Format: Article
Language:English
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Letter
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Summary:Inhibition of VEGFR-2 signaling pathway has already become one of the most promising approaches for the treatment of cancer. In this study, we describe the design, synthesis, and biological evaluation of a new series of naphthamides as potent inhibitors of VEGFR-2. Among these compounds, 14c exhibited high VEGFR-2 inhibitory potency in both enzymatic and HUVEC cellular proliferation assays, with IC50 values of 1.5 and 0.9 nM, respectively. Kinase selectivity profiling revealed that 14c was a multitargeted inhibitor, and it also exhibited good potency against VEGFR-1, PDGFR-β, and RET. Furthermore, 14c effectively blocked tube formation of HUVEC at nanomolar level. Overall, 14c might be a promising candidate for the treatment of cancer.
ISSN:1948-5875
1948-5875
DOI:10.1021/ml5000417