Discovery of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors

NWIPB OpenIR

	Discovery of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors
	Lv, Yongcong 1; Li, Mengyuan 2,3; Cao, Sufen 1,4; Tong, Linjiang 2; Peng, Ting 2; Wei, Lixin 3; Xie, Hua 2; Ding, Jian 2; Duan, Wenhu 1; Xie, H (reprint author), Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China.
	2015
发表期刊	MEDCHEMCOMM
卷号	6 期号:7 页码:1375-1380
文章类型	Article
摘要	Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive strategy for the treatment of cancer. Herein, we describe the design, synthesis, and biological evaluation of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors. Among the new derivatives, compound 3k exhibited high VEGFR-2 inhibitory potency in both enzymatic and VEGF-induced HUVEC cellular proliferation assays (IC50 = 0.5 and 9.8 nM, respectively). Kinase selectivity profiling revealed that 3k was a highly selective VEGFR-2 inhibitor. Moreover, 3k effectively inhibited angiogenesis in HUVEC tube formation assay.; Vascular endothelial growth factor receptor-2 (VEGFR-2) plays an important role in tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged as an attractive strategy for the treatment of cancer. Herein, we describe the design, synthesis, and biological evaluation of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors. Among the new derivatives, compound 3k exhibited high VEGFR-2 inhibitory potency in both enzymatic and VEGF-induced HUVEC cellular proliferation assays (IC50 = 0.5 and 9.8 nM, respectively). Kinase selectivity profiling revealed that 3k was a highly selective VEGFR-2 inhibitor. Moreover, 3k effectively inhibited angiogenesis in HUVEC tube formation assay.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
关键词[WOS]	ENDOTHELIAL GROWTH-FACTOR ; RENAL-CELL CARCINOMA ; FACTOR RECEPTOR ; KINASE INHIBITORS ; ANGIOGENESIS ; CANCER ; DISEASE
收录类别	SCI
语种	英语
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal
WOS记录号	WOS:000357786200020
引用统计	被引频次：7[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://210.75.249.4/handle/363003/5474
专题	中国科学院西北高原生物研究所
通讯作者	Xie, H (reprint author), Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China.
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Med Chem, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai 81008, Peoples R China 4.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China
推荐引用方式 GB/T 7714	Lv, Yongcong,Li, Mengyuan,Cao, Sufen,et al. Discovery of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors[J]. MEDCHEMCOMM,2015,6(7):1375-1380.
APA	Lv, Yongcong.,Li, Mengyuan.,Cao, Sufen.,Tong, Linjiang.,Peng, Ting.,...&Xie, H .(2015).Discovery of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors.MEDCHEMCOMM,6(7),1375-1380.
MLA	Lv, Yongcong,et al."Discovery of anilinopyrimidine-based naphthamide derivatives as potent VEGFR-2 inhibitors".MEDCHEMCOMM 6.7(2015):1375-1380.