title: Synthesis and evaluation of nicotinamide derivative as anti-angiogenic agents.
abstract: Previously, we have found that BRN-103, a nicotinamide derivative, inhibits vascular endothelial growth factor (VEGF)-mediated angiogenesis signaling in human endothelial cells. During our continuous efforts to identify more potent anti-angiogenic agents, we synthesized various nicotinamide derivatives and evaluated their anti-angiogenic effects. We found that 2-{1-[1-(6-chloro-5-fluoropyrimidin-4-yl)ethyl]piperidin-4-ylamino}-N-(3-chlorophenyl) pyridine-3-carboxamide (BRN-250) significantly inhibited human umbilical vascular endothelial cells (HUVECs) proliferation, migration, tube formation, and microvessel growth in a concentration range of 10-100 nM. Furthermore, BRN-250 inhibited the VEGF-induced phosphorylation and intracellular tyrosine kinase activity of VEGF receptor 2 (VEGFR2) and the activation of its downstream AKT pathway. Taken together, these findings suggest that BRN-250 be considered a potential lead compound for cancer therapy.
authors: Department of Pharmaceutical Biochemistry, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors: Hye-Eun
authors: HE
authors: Choi
authors: Jung-Hye
authors: JH
authors: Choi
authors: Jae Yeol
authors: JY
authors: Lee
authors: Je Hak
authors: JH
authors: Kim
authors: Ji Han
authors: JH
authors: Kim
authors: Joon Kwang
authors: JK
authors: Lee
authors: Gyu Il
authors: GI
authors: Kim
authors: Yong
authors: Y
authors: Park
authors: Yong Ha
authors: YH
authors: Chi
authors: Soo Heui
authors: SH
authors: Paik
authors: Joo Han
authors: JH
authors: Lee
authors: Kyung-Tae
authors: KT
authors: Lee
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009536:Niacinamide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042442:Vascular Endothelial Growth Factors; D009536:Niacinamide