摘要
目的为受体相互作用蛋白激酶1(RIPK1)抑制剂的开发及作用机制研究提供参考。方法采用计算机检索2005年至2024年PubMed、Web of Science、中国知网等数据库中RIPK1抑制剂的相关研究文献,总结RIPK1的结构、生物学功能与影响疾病,以及其抑制剂的分类。结果RIPK1为包含671个氨基酸的多功能蛋白,通过其激酶结构域、调节区域、死亡结构域、受体相互作用蛋白同型相互作用基序(RHIM)结构域在细胞死亡、炎性反应、肿瘤免疫反应中发挥重要作用。RIPK1与多发性硬化症、肌萎缩性侧索硬化症等慢性神经退行性疾病,炎症性肠病、银屑病等免疫和自身炎症性疾病,胶质母细胞瘤、黑色素瘤等肿瘤的发生与发展密切相关。基于作用构象和结合位点,RIPK1可分为Ⅰ型、Ⅱ型、Ⅲ型三磷酸腺苷竞争性抑制剂;基于化学结构,RIPK1可分为Necrostatin-1(Nec-1)及其衍生物类、苯并氧氮杂酮类、二氢吡唑类、苯并噻唑类、天然产物类及其衍生物类RIPK1抑制剂。结论RIPK1抑制剂研究在分子机制、构效关系及药物设计方面取得了显著进展,在基础研究与临床应用中有广阔前景。随着对RIPK1生物学功能的深入理解及新一代抑制剂的研发,RIPK1抑制剂有望为多种疾病提供新的治疗策略。
Objective To provide a reference for the development and mechanism of receptor-interacting protein kinase 1(RIPK1)inhibitors.Methods Researches on RIPK1 inhibitors in the PubMed,Web of Science,and CNKI databases were searched from 2005 to 2024.The structure,the biological functions,effects on diseases,and the classification of RIPK1 inhibitors were summarized.Results RIPK1 is a multifunctional protein containing 671 amino acids,which plays an important role in cell death,inflammatory response,and tumor immune response through its kinase domain,regulatory domain,death domain,and receptor-interacting protein kinase homotypic interaction motif(RHIM)domain.RIPK1 is closely related to the occurrence and development of chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis,immune and autoimmune inflammatory diseases such as inflammatory bowel disease and psoriasis,and tumors such as glioblastoma and melanoma.Based on its conformational and binding sites,RIPK1 can be classified into typeⅠ,typeⅡ,and typeⅢadenosine triphosphate competitive inhibitors.Based on their chemical structures,RIPK1 inhibitors can be classified into Necrostatin-1(Nec-1)and its derivatives,benzodiazepines,dihydropyrazoles,benzothiazoles,natural products and their derivatives.Conclusion Researches on RIPK1 inhibitors have made significant progress in molecular mechanisms,structure-activity relationships,and drug design,and RIPK1 inhibitors have broad prospects in basic research and clinical applications.With a deeper understanding of the biological functions of RIPK1 and the development of new generation inhibitors,RIPK1 inhibitors are expected to provide new treatment strategies for various diseases.
作者
李赐勤
杨全军
朱馨婷
韩冷
景凌洁
郭澄
LI Ciqin;YANG Quanjun;ZHU Xinting;HAN Leng;JING Lingjie;GUO Cheng(Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200032,China;School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)
出处
《中国药业》
2026年第1期6-13,共8页
China Pharmaceuticals
基金
国家自然科学基金[82274151]。
