Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective

被引:253
作者
Bongarzone, Salvatore [1 ]
Savickas, Vilius [1 ]
Luzi, Federico [1 ]
Gee, Antony D. [1 ]
机构
[1] Kings Coll London, Kings Hlth Partners, Div Imaging Sci & Biomed Engn, St Thomas Hosp, London SE1 7EH, England
基金
英国惠康基金; 英国医学研究理事会; 英国工程与自然科学研究理事会;
关键词
END-PRODUCTS RAGE; AMYLOID-BETA PEPTIDE; CELL-SURFACE RECEPTOR; NF-KAPPA-B; ALZHEIMERS-DISEASE; SOLUBLE RECEPTOR; CYTOPLASMIC DOMAIN; NEURITE OUTGROWTH; SIGNALING PATHWAY; OXIDATIVE STRESS;
D O I
10.1021/acs.jmedchem.7b00058
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The receptor for advanced glycation endproducts (RAGE) is an ubiquitous, transmembrane, immunoglobulin-like receptor that exists in multiple isoforms and binds to a diverse range of endogenous extracellular ligands and intracellular effectors. Ligand binding at the extracellular domain of RAGE initiates a complex intracellular signaling cascade, resulting in the production of reactive oxygen species (ROS), immunoinflammatory effects, cellular proliferation, or apoptosis with concomitant upregulation of RAGE itself. To date, research has mainly focused on the correlation between RAGE activity and pathological conditions, such as cancer, diabetes, cardiovascular diseases, and neurodegeneration. Because RAGE plays a role in many pathological disorders, it has become an attractive target for the development of inhibitors at the extracellular and intracellular domains. This review describes the role of endogenous RAGE ligands/effectors in normo- and pathophysiological processes, summarizes the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.
引用
收藏
页码:7213 / 7232
页数:21
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