Azeliragon

An orally bioavailable small molecule inhibitor of RAGE; inhibits sRAGE from binding to RAGE ligands, S100b, amphoterin and carboxymethyl-lysine; has been shown to inhibit the binding of sRAGE to Aβ1-42 in a fluorescent polarization assay; reduces accumulation in the spleen of Aβ peptides and the expression of IL-6 and macrophage colony stimulating factor, reduces both inflammatory markers (TNF-α, TGF-β and IL-1) and CNS amyloid deposition.Alzheimer's Disease Phase 3 Clinical (In Vitro) :Azeliragon (4 nM; 16 hours; T cells) treatment inhibits of wild type mice (WT) but not the deletion of the receptor (RAGE-/- mice) T cells and significant reduction in the production of IFN-γ. (In Vivo) :Azeliragon (100 mcg/d; intraperitoneal injection; every day) treatment reduces syngeneic islet graft and islet allograft in NOD and B6 mice (Islets were isolated from young prediabetic NOD/LtJ mice and transplanted into NOD mice with spontaneous diabetes; islets were isolated from WT BALB/c mice and transplanted into B6 mice with diabetes) .