靶向抗肿瘤化合物FAPα抑制剂的构效关系研究

探讨靶向抗肿瘤化合物FAPα抑制剂的构效关系，继而在此基础上进行虚拟筛选以期得到FAPα抑制剂特别是选择性抑制剂的候选化合物，并利用体内外实验进行验证是本课题主要的研究内容。..FAPα具有特异的肿瘤细胞表达性以及抑制其活性能够间接抑制肿瘤增值等特点，将其作为肿瘤靶向治疗药物的靶点具有一定的理论依据。鉴于FAPα抑制剂具有开发成为抗肿瘤药物的潜力，同时缺乏其系统的构效关系研究。因此本课题以FAPα抑制剂为研究目标，采用计算机辅助药物设计与体内外实验相结合的方法，拟进行FAPα抑制剂构效关系的研究。以期阐明FAPα抑制剂与其受体之间的关键相互作用，为FAPα抑制剂以及其选择性抑制剂的先导化合物的发现奠定基础。

The major objective of this study is to explore the SAR (Structure-Activity Relationship) of FAPα inhibitors as the targeted antitumor compounds. Base on the SAR, the virtual screening and in vitro/vivo experimental verifications are also taken to discover the new candidates of FAPα inhibitors especially the selective inhibitors..FAPα is highly expressed in most of tumors, meantime the inhibition of its activity can suppress the tumor cell proliferation. These two significant characteristics of FAPα make it be the valuable potential target of antitumor compounds. As it is hopeful to develop the inhibitors of FAPα to be the potential antitumor drugs and there is still no systematic research about the SAR of FAPα inhibitors. The studies are carried out for discussing the SAR of FAPα inhibitors by QSAR model, pharmacophore model and docking followed by in vitro/vivo experimental verification. The result of this study would be helpful to clarify the important interaction between FAPα and its inhibitors. Simultaneously, the discovery of FAPα inhibitors and its selective inhibitors will be also benefit from the SAR research.