Identification of novel angiogenesis inhibitors

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• 作者：Jayalakshmi Sridhar ; Nagaraju Akula ; Dakshanamurthy Sivanesan ; Madhusudhanan Narasimhan ; Appu Rathinavelu and Nagarajan Pattabiraman
• 关键词：VEGFR ; Kinase inhibitor ; Angiogenesis ; Drug discovery
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：15
• 期：18
• 页码：4125-4129
• 全文大小：911 K

文摘

Vascular endothelial growth factor (VEGF) is a key stimulant of angiogenesis, which is the process of generating new capillary blood vessels. Inhibition of the vascular endothelial growth factor receptor (VEGFR) kinase is known to result in blockage of angiogenesis. A pharmacophore was developed based on the binding of ATP to the hinge region of the kinase domain of VEGFR and a database search of 18,000 compounds was conducted. Selected hits were assessed for their ability to limit the induction of web-like network of capillary tubes by the human umbilical vascular endothelial cells. Two compounds (1 and 4) showed good inhibitory ability to prevent sprouting and closed polygon formation of the tubular networks, promising them to be lead compounds. Compound 4 showed 60 % inhibition at 0.05 μM.