FPS-ZM1 is a high-affinity RAGE specific inhibitor with a Ki of 25 nM. FPS-ZM1 blocks Aβ binding to the V domain of RAGE and inhibited Aβ40- and Aβ42-induced cellular stress in RAGE-expressing cells in vitro. 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.
FPS-ZM1 is nontoxic to mice and readily crossed the blood-brain barrier (BBB) in vivo. FPS-ZM1 effectively controls progression of an Aβ-mediated brain disorder and the related neurovascular and cognitive dysfunction in 17-month-old APPsw/0 mice with fully developed Aβ and amyloid pathology by blocking RAGE actions at the BBB and in brain.
|Cell lines||CHO cells|
|Preparation method||CHO cells are treated for 72 hours with different concentrations of inhibitors ranging from 10 nM to 10 μM. The cellular toxicity was determined using the CCK-8 Assay Kit.|
|Concentrations||10 nM to 10 μM|
|Incubation time||72 h|
|Animal models||C57BL/6 mice|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO: ≥ 20 mg/mL|
Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-β Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus.
Hong Y, et al. Neurochem Res. 2016 May;41(5):1192-9. PMID: 26738988.
A multimodal RAGE-specific inhibitor reduces amyloid β-mediated brain disorder in a mouse model of Alzheimer disease.
Deane R, et al. J Clin Invest. 2012 Apr;122(4):1377-92. PMID: 22406537.
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