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

被引：14
|
作者：
Lv, Yongcong [1 ]
Li, Mengyuan [2 ,3 ]
Liu, Ting [1 ,4 ]
Tong, Linjiang [2 ]
Peng, Ting [2 ]
Wei, Lixin [3 ]
Ding, Jian [2 ]
Xie, Hua [2 ]
Duan, Wenhu [1 ]
机构：
[1] Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China
[3] Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai 81008, Peoples R China
[4] Nanchang Univ, Coll Med, Nanchang 330066, Jiangxi, Peoples R China
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2014年 / 5卷 / 05期
基金：
中国国家自然科学基金;
关键词：
Angiogenesis; HUVEC; inhibitor; naphthamide; VEGFR-2; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; FACTOR RECEPTOR; CANCER; ANGIOGENESIS; DISEASE;
D O I：
10.1021/ml5000417
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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-beta, 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.
引用
收藏
页码：592 / 597
页数：6
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