黄连为“消渴”要药，临床使用广泛，而其作用机制尚不清晰、作用靶点不明确。本项目在团队长期研究黄连治疗糖尿病的基础上，整合参与单位拥有的药物发现领域前沿的DNA编码化合物库核心技术，首次将该技术应用于中药作用靶点发现与活性成分结构修饰，开展川产黄连治疗糖尿病的作用机制及创新药物发现研究。项目利用DNA编码黄连化学成分，垂钓作用靶点，辅以代谢组学和蛋白组学验证，完善黄连治疗糖尿病作用机制；反向筛选与靶点高亲和的黄连化学成分，并进行细胞与动物模型的综合评价，揭示黄连治疗糖尿病的药效物质基础；关联药效组分与靶点的信息，进行组分配伍研究，以期发现多成分-多靶点的组分配伍候选创新中药；针对黄连中遴选出的先导化合物，利用DNA编码技术进行结构修饰研究，预期发现治疗糖尿病的候选创新药物。项目架构以DNA编码技术为核心的“作用靶点-药效机制-物质基础-创新药物开发”的药物发现模式，将为中药研究提供新思路。

Coptidis rhizoma has the ability to cure diabetes mellitus, however, the therapeutic mechanism and related target proteins are still unknown. Based on our previous diabetes mellitus treatment research and DNA encoded compound library (DEL) technology which is at the forefront of drug R&D occupied by our participants, we initially bring DEL into the procedures of identification of C. rhizoma’ target as well as optimization of constitutes with therapeutic activities to investigate the therapeutic mechanism and discover new drugs. During this study, targe proteins will be identified by DNA encoded compound molecular probes guided by metabonomics as well as proteomics firstly. After illustrate their mechanism, the target protein will be immobilized to reverse bind constitutes with more affinity from C. rhizoma to dig more compounds with hypoglycemic activity. Then, those active compounds will be evaluated by pharmacodynamic-toxicologic-pharmacological comprehensive system under cellular-anic multi-level to explain the material basis of C. rhizoma during its therapeutic process as well as the deduce the correlation informations between compounds and target proteins. On the one hand, research about component compatibility will be applied to develop new TCM-derived molecular formula with multiconstituents-multitargets, On the other hand, structural modification will be applied on those compounds with excellent overall performance and each derivatives will be encoded by DNA for next iterative screening. This study tries to find new compounds or molecular formula with druggability based on the DEL and offer a new strategy for relative innovation of TCM.