TY - JOUR
T1 - Targeting the Receptor for Advanced Glycation Endproducts (RAGE)
T2 - A Medicinal Chemistry Perspective
AU - Bongarzone, Salvatore
AU - Savickas, Vilius
AU - Luzi, Federico
AU - Gee, Antony D
PY - 2017/5/8
Y1 - 2017/5/8
N2 - 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 signalling 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. Since 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, summarises the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.
AB - 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 signalling 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. Since 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, summarises the current status of exogenous small-molecule inhibitors of RAGE and concludes by identifying key strategies for future therapeutic intervention.
KW - Journal Article
U2 - 10.1021/acs.jmedchem.7b00058
DO - 10.1021/acs.jmedchem.7b00058
M3 - Article
C2 - 28482155
SN - 0022-2623
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
ER -
