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Purity: ≥98%
FPS-ZM1 is a potent and high-affinity RAGE specific blocker with Ki value of 25 nM. It inhibits amyloid-β binding to RAGE, neurological damage and inflammation in the APP(sw/0) transgenic mouse model of AD. An increased level of advanced glycation end products (AGEs) is observed in brains of patients with Alzheimer's disease (AD). AGEs and receptor for AGEs (RAGE) play important roles in the pathogenesis of AD. FPS-ZM1 is not toxic to mice and can easily cross the blood-brain barrier. AGEs administration induced an-regulation of Abeta production, inflammation, and oxidative stress, and an increased escape latency of rats in the Morris water maze test, all of these are significantly reduced by FPS-ZM1 treatment. FPS-ZM1 might be a novel therapeutic agent to treat AD patients.
| ln Vitro |
Compared to its parent molecule FPS2, FPS-ZM1 inhibits Aβ/RAGE binding in CHO cells with an affinity that is about two times higher. Other recognized RAGE ligands, such as amphoterin and S100 calbindin B, are inhibited from binding to sRAGE by FPS-ZM1. When it comes to decreasing Aβ40-induced increases in BACE1 mRNA and protein levels as well as the generation of sAPPβ, the APP cleavage product of BACE1 that indicates BACE1 activity, FPS-ZM1 is more effective than FPS2 [1].
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| ln Vivo |
Mice cannot be poisoned by FPS-ZM1, and it easily penetrates the blood-brain barrier. In aged APPsw/0 mice overexpressing human Aβ precursor protein, an AD transgenic mouse model with established Aβ pathology, FPS-ZM1 inhibits RAGE-mediated influx of circulating Aβ40 into the brain and Aβ42 entry into the brain. FPS-ZM1 binds specifically to RAGE in the brain, suppressing microglial activation and neuroinflammatory responses while inhibiting β-secretase activity and Aβ production [1]. In AGEs rats, the levels of Aβ1-42 and Aβ1-40 were decreased by FPS-ZM1 treatment. It downregulates the AGEs-mediated increase in hippocampal pro-inflammatory cytokines and inhibits the AGEs-mediated increase in Aβ metabolism-related proteins. In rats with advanced ageing, FPS-ZM1 improves the antioxidant defense system and reduces the memory impairment caused by AGEs [2].
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| References |
[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 |
| Molecular Formula |
C20H22CLNO
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| Molecular Weight |
327.85
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| CAS # |
945714-67-0
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| Related CAS # |
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| SMILES |
C1CCC(CC1)N(CC2=CC=CC=C2)C(=O)C3=CC=C(C=C3)Cl
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.63 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.63 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.63 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (7.63 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0502 mL | 15.2509 mL | 30.5018 mL | |
| 5 mM | 0.6100 mL | 3.0502 mL | 6.1004 mL | |
| 10 mM | 0.3050 mL | 1.5251 mL | 3.0502 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 FPS-ZM1 and FPS2 inhibit Aβ/RAGE binding in cell-free and cell-based assays.J Clin Invest.2012 Apr;122(4):1377-92. |
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 FPS-ZM1 and FPS2 block RAGE-mediated Aβ BBB transport, Aβ pathology, and functional outcome in oldAPPsw/0mice.J Clin Invest.2012 Apr;122(4):1377-92. |
 Effects of FPS-ZM1 and FPS2 on BACE1 in brains of 17-month-oldAPPsw/0mice.J Clin Invest.2012 Apr;122(4):1377-92. |
 FPS-ZM1 and FPS2 control the neuroinflammatory response in 17-month-oldAPPsw/0mice.J Clin Invest.2012 Apr;122(4):1377-92. |
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