受体酪氨酸激酶FGFRs是肿瘤治疗的重要靶点，FGFR抑制剂通过与受体目标区域作用阻止FGFR介导的细胞增殖信号转导而发挥抗肿瘤作用。FGFR受体抑制剂基本为合成产物，筛选出天然FGFR受体抑制剂前景广阔。本课题组研究发现祖师麻中一类新的多异戊烯基黄烷类成分具有FGFRl抑制作用，与FGFRl蛋白共结晶抑制剂具有类似的氨基酸残基结合方式，能够发挥细胞周期阻滞作用，降低p65NF-κB的表达、JNK的磷酸化，但多异戊烯黄烷是直接作用于其靶蛋白JNK、NF-κB发挥细胞周期阻滞，还是通过依赖FGFR1及MAPK/JNK从而进一步抑制NF-κB的入核转运而调控下游靶蛋白发挥肿瘤作用等科学问题尚待阐明。因此项目具体内容涵括：①祖师麻中的多异戊烯黄烷类进行定向分离；②FGFR1抑制及抗肿瘤活性筛选；③基于FGFR1靶点及MAPK/NF-κB信号通路作用机制研究，为肿瘤靶向药物的研发提供新的理论依据。

Receptor tyrosine kinase FGFRs is one of the most important targets for cancer treatment，FGFR inhibitors exhibit anti-tumor effects by interacting with target area of receptor to prevent cell proliferation signal transduction mediated by FGFR. Most FGFR inhibitors are synthetic products, thereby there are broad prospects for screening of FGFR inhibitor from natural products. In our study, a series of polyprenylflavane isolated from Daphne giradii have been found to inhibit FGFR, and have a similar combination mode with the amino acid residues compared with FGFRl inhibitor. The compounds can reduce the expression of p65 and inhibit the phosphorylation of JNK. However, further investigations about the direct action of polyprenylflavane on their target proteins JNK, NF-κB to arrest cell cycle or depending on FGFR1 and MAPK/JNK and inhibiting nuclear import of NF-κB to prevent tumor growth should be conducted. So we will study the following aspects to this project the details of our research are including：①target separation of polyprenylflavane flavans from D. Giradii. ②Screening of compounds which have FGFR1 inhibition effect and anti-tumor activity. ③Mechanism research that based on FGFR1 targets and MAPK/NF-κB signaling pathway. For anti-tumor drugs research to provide new theoretical basis for the research and development of anti-tumor drugs.