Ki: 25 nM

FPS-ZM1 is a RAGE Inhibitor.

The receptor for advanced glycation end products (RAGE) belongs to the immunoglobulin superfamily. RAGE has an extracellular V domain binding multiple ligands. The ligand-RAGE interactions result in sustained cellular perturbation in chronic diseases including diabetes, inflammation, as well as AD.

In vitro: FPS-ZM1 was identified as a high-affinity inhibitor of the receptor for advanced glycation end products. FPS-ZM1 could block the binding of amyloid β (Aβ) protein to RAGE and inhibit Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells [1].

In vivo: Animal study found that FPS-ZM1 was nontoxic to mice and readily crossed the blood-brain barrier (BBB). In aged APPsw/0 mice overexpressing human Aβ-precursor protein, FPS-ZM1 could inhibit RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. FPS-ZM1 bound exclusively to RAGE In brain, which inhibited β-secretase activity and Aβ production and suppressed microglia activation and the neuroinflammatory response. Moreover, the blockade of RAGE actions at the BBB and in the brain could reduce Aβ40 and Aβ42 levels in brain in aged APPsw/0 mice [1].

Clinical trial: So far, no clinical study has been conducted.

Reference:
[1] Deane, R.,Singh, I.,Sagare, A.P., et al. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 122(4), 1377-1392 (2012).