摘要
晚期糖基化终末产物受体(receptor for advanced glycation endproducts,RAGE)是一种普遍存在的多亚型跨膜免疫球蛋白样受体,可与多种胞外配体结合,激活胞内效应分子,启动复杂的胞内信号级联反应,引起细胞内氧化应激和炎症反应,导致细胞功能紊乱,与癌症、糖尿病、心血管疾病及神经变性疾病等密切相关。寻找靶向RAGE的拮抗剂或许有望改善并治疗癌症、糖尿病、心血管疾病、神经变性疾病等多种相关性疾病。本文综述了靶向RAGE的外源性小分子拮抗剂的结构特点、结合区域及研究现状,为靶向RAGE的药物发现、确定未来治疗干预的策略提供了思路,具有一定借鉴意义。
The receptor for advanced glycation endproducts(RAGE),a common immunoglobulin-like receptor with multiple isoforms,can bind to various extracellular ligands and intracellular effectors,thus initiates intricate intracellular signaling cascade,especially the immunoinflammatory cascades and the production of reactive oxygen species(ROS).RAGE activity is implicated in various pathological conditions,including cancer,diabetes,cardiovascular diseases and neurodegeneration.The finding of exogenous small-molecule inhibitors of RAGE may ameliorate the pathological progression.This review focuses on the current state of small-molecule RAGE inhibitors and classifies them by the binding domain and structure characteristics,which may show great benefits on RAGE-targeted drug discovery and development,and broaden our horizon of the related medical treatments.
作者
郑玲
李虹
张文生
ZHENG Ling;LI Hong;ZHANG Wen-sheng(Faculty of Geographical Science,Beijing Normal University,Engineering Research Center of Natural Medicine,Ministry o f Education,Beijing100815,China;Faculty of Geographical Science,Beijing Normal University,Beijing Key Laboratory of Traditional Chinese Medicine Protection and Utilization,Beijing 100875,China;Beijing Normal University,Zhuhai Branch of State Key Laboratory of Earth Surface Processes and Resource Ecology,Zhuhai 519000,China)
出处
《中国药物化学杂志》
CAS
CSCD
2021年第2期142-151,共10页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金项目(81771152)。
关键词
晚期糖基化终末产物受体
小分子
拮抗剂
结合区域
药物发现
receptor for advanced glycation endproducts
small-molecule
inhibitor
binding domain
drug discovery and development
