title: BRN-103, a novel nicotinamide derivative, inhibits VEGF-induced angiogenesis and proliferation in human umbilical vein endothelial cells.
abstract: Anti-angiogenesis is regarded as an effective strategy for cancer treatment, and vascular endothelial growth factor (VEGF) plays a key role in the regulations of angiogenesis and vasculogenesis. In the present study, the authors synthesized five novel nicotinamide derivatives which structurally mimic the receptor tyrosine kinase inhibitor sunitinib and evaluated their anti-angiogenic effects. Transwell migration assays revealed that 2-(1-benzylpiperidin-4-yl) amino-N-(3-chlorophenyl) nicotinamide (BRN-103), among the five derivatives most potently inhibited VEGF-induced human umbilical vein endothelial cells (HUVECs). In addition, BRN-103 dose-dependently inhibited VEGF-induced migration, proliferation, and capillary-like tube formation of HUVECs and vessel sprouting from mouse aortic rings. To understand the molecular mechanisms responsible for these activities, the authors examined the effect of BRN-103 on VEGF signaling pathways in HUVECs. BRN-103 was found to suppress the VEGF-induced phosphorylation of VEGF receptor 2 (VEGR2) and the activations of AKT and eNOS. Taken together, these results suggest that BRN-103 inhibits VEGF-mediated angiogenesis signaling in human endothelial cells.
authors.affiliation: Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hye-Eun
authors.initials: HE
authors.lastname: Choi
authors.forename: Min-Sang
authors.initials: MS
authors.lastname: Yoo
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
authors.forename: Je Hak
authors.initials: JH
authors.lastname: Kim
authors.forename: Ji Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Joon Kwang
authors.initials: JK
authors.lastname: Lee
authors.forename: Gyu Il
authors.initials: GI
authors.lastname: Kim
authors.forename: Yong
authors.initials: Y
authors.lastname: Park
authors.forename: Yong Ha
authors.initials: YH
authors.lastname: Chi
authors.forename: Soo Heui
authors.initials: SH
authors.lastname: Paik
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology
chemical_list: C569517:2-(1-benzylpiperidin-4-yl)amino-N-(3-chlorophenyl)nicotinamide; D020533:Angiogenesis Inhibitors; D010880:Piperidines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide