| Bioactivity | FPS-ZM1 is a high-affinity RAGE inhibitor with a Ki of 25 nM. | ||||||||||||
| Target | Ki: 25 nM (RAGE) | ||||||||||||
| Invitro | FPS-ZM1 inhibits Aβ/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 Aβ40-induced increases inBACE1 mRNA and protein levels and the generation of sAPPβ, 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 APPsw/0 mice overexpressing human Aβ-precursor protein, a transgenic mouse model of AD with established Aβ pathology, FPS-ZM1 inhibits RAGE-mediated influx of circulating Aβ40 and Aβ42 into the brain. In brain, FPS-ZM1 binds exclusively to RAGE, which inhibits β-secretase activity and Aβ production and suppresses microglia activation and the neuro-inflammatory response[1]. FPS-ZM1 treatment reduces the level of Aβ1-40 and Aβ1-42 in AGEs Rats. It Inhibits AGEs-mediated increase of Aβ-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]. | ||||||||||||
| Name | FPS-ZM1 | ||||||||||||
| CAS | 945714-67-0 | ||||||||||||
| Formula | C20H22ClNO | ||||||||||||
| Molar Mass | 327.85 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Deane R, et al. A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012 Apr;122(4):1377-92. [2]. Hong Y, et al. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus. Neurochem Res. 2016 May;41(5):1192-9. [3]. Lian YJ, et al. Ds-HMGB1 and fr-HMGB induce depressive behavior through neuroinflammation in contrast to nonoxid-HMGB1. Brain Behav Immun. 2017 Jan;59:322-332. |