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

ABSTRACT: 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-?, 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.

SUBMITTER: Lv Y

PROVIDER: S-EPMC4027589 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Lv Yongcong Y Li Mengyuan M Liu Ting T Tong Linjiang L Peng Ting T Wei Lixin L Ding Jian J Xie Hua H Duan Wenhu W

ACS medicinal chemistry letters 20140224 5

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 mul ...[more]

PMID: 24900886

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