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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 Experiment | |
|---|---|
| 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 Experiment | |
|---|---|
| Animal models | C57BL/6 mice |
| Formulation | PBS |
| Dosages | 1 mg/kg |
| Administration | i.v. |
| Molecular Weight | 327.85 |
| Formula | C20H22ClNO |
| CAS Number | 945714-67-0 |
| Solubility (25°C) | DMSO ≥ 33 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
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