饶燏 Yi Rao

饶燏教授从事新药发现的化学生物学研究，长期致力于蛋白质靶向降解技术（PROTAC）的开发和应用。研究工作主要围绕’抗重大疾病先导化合物的发现和优化’开展。代表性论文发表于Nature Chemical Biology, Nature Communications, Cell Research, Leukemia, Journal of Medicinal Chemistry, Cell Discovery, Protein & Cell等国际学术期刊。受邀参编首部PROTAC蛋白降解专著”Protein Degradation with New Chemical Modalities”的编写。饶燏实验室通过发展新型小分子靶向蛋白降解技术希望解决若干长期困扰的生物学和医学问题，并取得了一系列的研究进展：1）基于靶向蛋白降解技术PROTAC建立BRD4相分离研究新方法（Cell Discovery 2023）；2）提出了PROTAC和分子胶协同应用的模式。根据PROTAC和分子胶的特点首次设计合成了新型双靶、双机制的降解剂，为靶向降解技术的发展提出了新的思路（Cell Research 2021）；3）实现难成药靶点的药物开发，设计合成首例选择性CDK2降解剂，实现AML高效且低毒的分化治疗（Nature Chemical Biology 2021）；4）构建高效的BTK降解剂，解决临床中出现的Ibrutinib耐药问题（Cell Research 2018；Leukemia 2019）；5）构建PROTACs系统性敲除模型，快速可逆实现非人灵长类动物体内蛋白敲除（Cell Discovery 2019）。研究疾病领域主要包括恶性肿瘤，感染及老年退行性疾病。重点研究方向包括以下方面：发展小分子靶向蛋白降解技术（PROTAC/分子胶等）进行靶向蛋白降解及相关药物研究；依据蛋白质三维结构进行抗肿瘤、抗感染疾病小分子化合物的设计、合成与开发；具有高生物活性小分子的化学合成及作为分子探针应用于化学生物学研究。

Professor Yi Rao is engaged in chemical biology research for new drug discovery, with long-term dedication to the development and application of protein targeting degradation technology (PROTAC). Research work mainly focuses on “discovery and optimization of lead compounds against major diseases”. Representative papers have been published in international academic journals such as Nature Chemical Biology, Nature Communications, Cell Research, Leukemia, Journal of Medicinal Chemistry, Cell Discovery, and Protein & Cell. Invited to participate in writing the first PROTAC protein degradation monograph “Protein Degradation with New Chemical Modalities”. The Rao Yi laboratory aims to solve several long-standing biological and medical problems through developing novel small molecule targeted protein degradation technologies, achieving a series of research advances: 1) Established a new method for BRD4 phase separation research based on targeted protein degradation technology PROTAC (Cell Discovery 2023); 2) Proposed a synergistic application mode of PROTAC and molecular glue. Based on the characteristics of PROTAC and molecular glue, first designed and synthesized a novel dual-target, dual-mechanism degrader, proposing new ideas for the development of targeted degradation technology (Cell Research 2021); 3) Achieved drug development for difficult-to-drug targets, designed and synthesized the first selective CDK2 degrader, achieving efficient and low-toxicity differentiation therapy for AML (Nature Chemical Biology 2021); 4) Constructed efficient BTK degraders to solve the Ibrutinib resistance problem in clinical practice (Cell Research 2018; Leukemia 2019); 5) Constructed PROTAC systematic knockout models, rapidly and reversibly achieving protein knockout in non-human primates (Cell Discovery 2019). Research disease areas mainly include malignant tumors, infections, and age-related degenerative diseases. Key research directions include: developing small molecule targeted protein degradation technologies (PROTAC/molecular glue, etc.) for targeted protein degradation and related drug research; designing, synthesizing and developing anti-tumor and anti-infection small molecule compounds based on protein three-dimensional structures; chemical synthesis of highly bioactive small molecules and their application as molecular probes in chemical biology research.

1. Y. Shi, Y. Liao, Q. Liu, Z. Ni, Z. Zhang, M. Shi, P. Li*, H. Li*, Y. Rao*, ‘BRD4-targeting PROTAC as a unique tool to study biomolecular condensates’, Cell Discovery, 2023, 9, DOI: 10.1038/s41421-023-00544-0.
2. Z. Yang, Y. Sun, Z. Ni, C. Yang, Y. Tong, Y. Liu, H. Li and Y. Rao*, ‘Merging PROTAC and molecular glue for degrading BTK and GSPT1 proteins concurrently’, Cell Research, 2021, 25, 1315-1318.
3. L. Wang, X. Shao, T. Zhong, Y. Wu, A. Xu, X. Sun, H. Gao, Y. Liu, T. Lan, Y. Tong, X. Tao, W. Du, W. Wang, Y. Chen, T. Li, X. Meng, H. Deng, B. Yang, Q. He, M. Ying*, Y. Rao*, ‘Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy’, Nature Chemical Biology, 2021, 16.