FPS-ZM1

945714-67-0

C20H22ClNO

DMSO : >= 100 mg/mL (305.02 mM); H2O : < 0.1 mg/mL (insoluble)

Neuronal Signaling

FPS-ZM1 is a high-affinity RAGE specific inhibitor with a K_i of 25 nM. IC50 & Target: Ki: 25 nM (RAGE)^[1] In Vitro: FPS-ZM1 inhibits Abeta/RAGE binding in CHO cells with approximately 2-fold greater affinity than its parent molecule, FPS2. FPS-ZM1 inhibits binding of other known RAGE ligands to sRAGE, including S100 calcium-binding protein B and amphoterin. FPS-ZM1 is more effective than FPS2 in reducing Abeta40-induced increases inBACE1 mRNA and protein levels and the generation of sAPPbeta, an APP cleavage product of BACE1 indicative of BACE1 activity^[1]. In Vivo: FPS-ZM1 is nontoxic to mice and readily crossed the blood-brain barrier. In aged APP^sw/0 mice overexpressing human Abeta-precursor protein, a transgenic mouse model of AD with established Abeta pathology, FPS-ZM1 inhibits RAGE-mediated influx of circulating Abeta40 and Abeta42 into the brain. In brain, FPS-ZM1 binds exclusively to RAGE, which inhibits beta-secretase activity and Abeta production and suppresses microglia activation and the neuro-inflammatory response^[1]. FPS-ZM1 treatment reduces the level of Abeta1-40 and Abeta1-42 in AGEs Rats. It Inhibits AGEs-mediated increase of Abeta-metabolism-related proteins and downregulates AGEs-mediated increase of pro-inflammatory cytokines in the hippocampus. FPS-ZM1 up-Regulates anti-oxidant defense system and attenuated AGEs induced memory impairment in AGEs rats^[2].