title: 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-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.
authors.affiliation: Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Yongcong
authors.initials: Y
authors.lastname: Lv
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China ; Northwest Institute of Plateau Biology, Chinese Academy of Sciences , 23 Xinning Road, Qinghai 81008, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China ; Medical College of Nanchang University , 461 Bayi Road, Nanchang, Jiangxi 330066, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Liu
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Tong
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.affiliation: Northwest Institute of Plateau Biology, Chinese Academy of Sciences , 23 Xinning Road, Qinghai 81008, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wei
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.affiliation: Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 555 Zu Chong Zhi Road, Shanghai 201203, China.
authors.forename: Wenhu
authors.initials: W
authors.lastname: Duan
keywords: Angiogenesis; HUVEC; VEGFR-2; inhibitor; naphthamide