RAGE 229

RAGE 229 is an orally active ctRAGE-DIAPH1 inhibitor. RAGE 229 can inhibit the intracellular RAGE signaling by inhibiting the interaction between the cytoplasmic tail of RAGE(ctRAGE) and Diaphanous-1(DIAPH1).

RAGE229 has affinity for the ctRAGE with K_Dvalue of 2 nM and inhibits SMC migration with an IC₅₀ value of 26 nM^[1].

RAGE229 (oral gavage, 5 mg/kg, twice daily, for 4 days) assuages short- and long-term complications of diabetes in mice^[1].
RAGE229 (oral or iv.; 150, 50 and 15 ppm chow; 30, 10, and 3 mg/kg per day per mouse) (5 mg/kg, ip. , every 12 hours for four total doses) reduces plasma concentrations of TNF-α, IL-6, and CCL2/JE-MCP1 in diabetic mice, and reduces pathological and functional indices of diabetes-like kidney disease^[1].

References:
[1]. Michaele B Manigrasso, et al. Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice. Sci Transl Med. 2021 Nov 24;13(621):eabf7084.