RAGE229

RAGE229 is an experimental small-molecule antagonist of the intracellular interaction between the cytoplasmic tail of the receptor for advanced glycation end products (ctRAGE, encoded by AGER) and the formin protein Diaphanous-1 (DIAPH1). By competitively inhibiting binding of DIAPH1 to ctRAGE, RAGE229 blocks downstream RAGE-mediated inflammatory signal transduction without affecting blood glucose levels, thereby reducing inflammatory tissue damage, ischemia–reperfusion injury, and diabetic complications in preclinical models.[1][3][6][10] In mouse models of type 1–like and type 2–like diabetes, oral, intraperitoneal, or topical administration of RAGE229 reduced cardiac infarct size, accelerated diabetic wound healing, and lessened structural and functional kidney injury, while lowering circulating inflammatory mediators such as TNF-α, IL-6, and CCL2/JE-MCP1.[1][3][5][6] Structurally, RAGE229 (N-(4-(7-cyano-4-(morpholin-4-ylmethyl)quinolin-2-yl)phenyl)acetamide) exhibits high affinity for ctRAGE (Kd ≈ 2 nM) and was developed as a first-generation chemical probe for targeting the RAGE–DIAPH1 signaling axis.[1][3][6][10]

Other names

N-(4-(7-cyano-4-(morpholin-4-ylmethyl)quinolin-2-yl)phenyl)acetamide