FPS-ZM1
(Synonyms: RAGE Antagonist) 目录号 : GC15105
A high-affinity inhibitor of RAGE
Cas No.:945714-67-0
Sample solution is provided at 25 µL, 10mM.
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).
Kinase experiment: | Human sRAGE is immobilized (10 μg/mL) overnight at 4°C in 96-well microtiter plates and blocked with 3% bovine serum albumin. 125I-labeled Aβ40, HMGB1, or S100B at 5 nM in the absence and presence of various concentrations of FPS2 or FPS-ZM1 (10 to 1,000 nM) is added to the wells containing immobilized sRAGE and incubated for 1 hour at room temperature in PBS. Wells are washed with cold PBS to remove unbound radiolabeled ligands, and the radioactivity is analyzed[1]. |
Cell experiment: | To determine whether FPS2 and FPS-ZM1 are toxic to CHO cells, the cells are treated for 72 hours with different concentrations of inhibitors ranging from 10 nM to 10 μM. The cellular toxicity is determined using the WST-8 Assay Kit[1]. |
Animal experiment: | Rats: Starting from 1 week before intrahippocampal injection, FZM1 and AGEs+FZM1 rats are intraperitoneally injected with FPS-ZM1 (1 mg/kg/d at a volume of 2 mL) for 4 weeks; rats in the AGEs and the control groups are intraperitoneally injected with normal saline with the same volume for 4 weeks. Three weeks after AGEs intrahippocampal injection, the escape latency time of rats is assayed with Morris water maze test, and then all rats are sacrificed[2]. Mice: FPS2 or FPS-ZM1 are administered i.v. (1 mg/kg) via the femoral vein and arterial blood samples (30 μL) collected at 1, 5, 10, 15, and 20 minutes via the cannulated femoral artery. Plasma is separated by centrifugation at 4°C and immediately stored at -80°C until analysis[1]. |
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. | |
| Cas No. | 945714-67-0 | SDF | |
| 别名 | RAGE Antagonist | ||
| 化学名 | 4-chloro-N-cyclohexyl-N-(phenylmethyl)-benzamide | ||
| Canonical SMILES | ClC1=CC=C(C(N(CC2=CC=CC=C2)C3CCCCC3)=O)C=C1 | ||
| 分子式 | C20H22ClNO | 分子量 | 327.9 |
| 溶解度 | ≥ 28.6mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0497 mL | 15.2486 mL | 30.4971 mL |
| 5 mM | 0.6099 mL | 3.0497 mL | 6.0994 mL |
| 10 mM | 0.305 mL | 1.5249 mL | 3.0497 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
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