申请人在天然药物化学领域从事学术研究工作，通过对40余种传统药用植物及其组织培养物的化学成分和生物活性进行系统深入研究，发现了百余种具有新颖结构骨架成分，及作用于糖尿病，癌症等重大疾病热点分子靶点的活性成分；结合结构修饰和作用机制研究深入探讨其构效关系，为创新药物研发奠定了坚实的物质基础。在本项目中，拟对糖尿病靶点PTP1B开展研究，在现已发现的结构新颖的先导化合物基础上，通过分子模拟方法，研究该类化合物的作用机制，开展化学修饰工作，并通过酶水平、细胞水平检测其生物学活性，研发创新药物。

The applicant is major in the research field of natural medicine chemistry. Up to date, He has investigated the chemical constituents and biological activities of more than 40 kinds of traditional medicinal plants, and have found over a hundred kinds of novel natural compounds, and bioactive compounds targeting the molecular targets of major diseases, such as diabetes, and cancer. The structure-activity relationship was also investigated by detailed chemical and mechanism study. These finding has laid a solid foundation for innovative drug development. In this project, we aim to discover PTP1B inhibitors based on the new structural lead compound previously found in our lab, through using molecular modeling method and chemical modification strategy and in vitro test, to elucidate their inhibitory activities as well as mechanism of action. Finally, a drug candidate would be obtained for diabetic’s therapy.