Therapeutic potential of targeting the receptor for advanced glycation end products (RAGE) by small molecule inhibitors

Receptor for advanced glycation end products (RAGE) is a 45 kDa transmembrane receptor of immunoglobulin family that can bind to various endogenous and exogenous ligands and initiate the inflammatory downstream signaling pathways. RAGE is involved in various disorders including cardiovascular and neurodegenerative diseases, cancer, and diabetes. This review summarizes the structural features of RAGE and its various isoforms along with their pathological effects. Mainly, the article emphasized on the translational significance of antagonizing the interactions of RAGE with its ligands using small molecules reported in the last 5 years and discusses future approaches that could be employed to block the interactions in the treatment of chronic inflammatory ailments. The RAGE inhibitors described in this article could prove as a powerful approach in the management of immune‐inflammatory diseases. A critical review of the literature suggests that there is a dire need to dive deeper into the molecular mechanism of action to resolve critical issues that must be addressed to understand RAGE‐targeting therapy and long‐term blockade of RAGE in human diseases.