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Recent research and development of DYRK1A inhibitors

Chinese Chemical Letters 2022年第4期33卷 1841-1849页

作者： Liyun Zhao Xuan Xiong Li Liu Qi Liang Rongsheng Tong Xuanlin Feng Lan Bai Jianyou Shi Personalized Drug Therapy Key Laboratory of Sichuan Province Sichuan Academy of Medical Science&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China College of Medicine Southwest Jiaotong UniversityChengdu 610031China Emergency Intensive Care Unit Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Academy of Medical Science&Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610072China

Dual specificity tyrosine phosphorylation regulated kinase 1 A(DYRK1 A) is an evolutionarily conserved protein kinase belonging to the CMGC kinase family, which is closely related to Down syndrome(DS)and Alzheimer’s disease(AD). In recent years, not only the treatment of diabetes, but also the treatment of cancer gradually focuses on targeting DYRK1 A. Therefore, a series of DYRK1 A inhibitors have been developed to treat relevant diseases and clarify their treatment mechanism furtherly. DYRK1 A inhibitors are mainly divided into natural products and synthetic compounds. Among them, harmine is an excellent DYRK1 A inhibitor. Therefore, the synthetic DYRK1 A inhibitors are mainly based on harmine, which greatly enriches the structure and quantity of DYRK1 A inhibitors. The interaction between the inhibitors and the DYRK1 A protein has a guiding significance in predicting the activity of the inhibitors, and plays an irreplaceable role in the design of the compounds. This paper mainly reviews DYRK1 A inhibitors found in recent years and their structure-activity relationship, looking forward to providing a theoretical basis for the development of DYRK1 A inhibitors.

关键词： DYRK1A inhibitor Natural product synthetic compound Alzheimer’s disease Down syndrome

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