胰腺癌细胞具有高放化疗耐受性与高转移性，而其所处的低氧环境是关键原因。开发低氧靶向的胰腺癌药物有望为胰腺癌提供新的治疗方案。目前低氧选择性的化合物很少，而天然产物BE-43547A2对胰腺癌Panc-1细胞系具有很强的低氧选择性。本课题拟在课题组发展的BE-43547A2高效全合成路线基础上，通过结构修饰、“双缓”策略成药性改造与细胞/动物水平的筛选，获得更优异的低氧靶向先导化合物；同时设计分子探针，探索BE-43547类化合物的作用靶点。课题不仅有望获得成药性高、低氧靶向的抗胰腺癌先导化合物，同时有望基于发现的靶点为低氧靶向药物的设计提供新的分子基础。

Tumor hypoxia is speculated as the main reason to cause therapeutic resistance and tumor metastasis in pancreatic cancer. Therefore, development of hypoxia-targeting drugs holds hope for pancreatic cancer therapy. However, it is very difficult to discover compounds with hypoxia selectivity. Natural product BE-43547A2 show significant hypoxia selectivity towards Panc-1 cell line. Based on our completed synthetic route of BE-43547A2, this project aims to obtain hypoxia-targeting lead compounds towards pancreatic cancer via medicinal modification and double sustained release strategy. Preliminary structure-activity relationship(SAR) against Panc-1 cell line will be concluded via cell/animal bioassay, and molecular probe will be designed and synthesized based on the SAR. Protein mass spectrum will be applied to investigate the target of BE-43547 family. This project may not only accomplish the SAR of BE-43547A2 against Panc-1, but also identify hypoxia-targeting lead compounds towards pancreatic cancer, and elucidate more information about the target structure for the design and synthesis of drugs with hypoxia selectivity.