FPS-ZM1 is non-toxic in mice and efficiently crosses the blood-brain barrier. In aged APPsw/0 mice, a transgenic model of Alzheimer's disease (AD) that overexpresses the human Aβ-precursor protein and exhibits established Aβ pathology, FPS-ZM1 blocks the RAGE-mediated import of circulating Aβ40 and Aβ42 into the brain. Within the brain, FPS-ZM1 exclusively targets RAGE, leading to the inhibition of β-secretase activity and consequent reduction in Aβ production. It also diminishes microglia activation and the neuroinflammatory response^[1].

Furthermore, FPS-ZM1 therapy decreases the concentrations of Aβ1-40 and Aβ1-42 in rats exposed to advanced glycation end products (AGEs). It counteracts the AGEs-induced augmentation of Aβ-metabolism-associated proteins and downregulates the AGEs-stimulated increase of pro-inflammatory cytokines in the hippocampus. Additionally, FPS-ZM1 enhances the antioxidant defense system and mitigates memory impairments induced by AGEs in these rats^[2].

FPS-ZM1 demonstrates a higher affinity for inhibiting Aβ/RAGE binding in CHO cells, nearly doubling the effectiveness compared to its precursor, FPS2. It also prevents the binding of other RAGE ligands, such as S100 calcium-binding protein B and amphoterin. FPS-ZM1 surpasses FPS2 in mitigating the Aβ40-triggered elevation of BACE1 mRNA and protein levels, as well as the production of sAPPβ, a cleavage product of APP by BACE1, indicating BACE1 enzymatic activity^[1].