Discovery of Novel Anti-tumour Agents for Specific Recognizing the G-quadruplex in 5'-Untranslated Region of Human Vascular Endothelial Growth Factor(hVEGF)
作者单位：中山大学药学院 School of PharmacyGuangdong Medical College Cancer Research UK Cambridge InstituteUniversity of CambridgeLi Ka Shing Centre
会议名称：《第九届全国核糖核酸学术讨论会》
会议日期：2016年
学科分类：1007[医学-药学(可授医学、理学学位)] 10[医学]
关 键 词：VEGF translational regulation G-quadruplex quinazoline derivative antitumor
摘 要：Angiogenesis is important in tumorigenesis and tumor *** vascular endothelial growth factor(h VEGF)is an angiogenic growth factor that plays a crucial role in tumor *** G-rich region within the 5’-untranslated region(5’-UTR)of h VEGF m RNA can form a‘switchable’RNA G-quadruplex structure that is essential for a cap-independent translation *** firstly screen our small-molecule library for binders of this *** a result,a novel quinazoline derivative compound 1shows a significant specific interaction with the G-tract and destabilizes the Gquadruplex *** experiments results reveal that compound 1 downregulates h VEGF translation,and significantly impedes tumor cells *** also find thatcompound1exhibitsan obvious tumor inhibiting activity in MCF-7 xenograft tumors,which may relate with its ability to reduce h VEGF *** findings provide a new way of h VEGF translational control through interacting with Gquadruplex structure in the 5’UTRby small molecules.