FPS-ZM1
(Synonyms: RAGE Antagonist) 目录号 : GC15105
FPS-ZM1是一种特异性RAGE抑制剂，Ki值为25nM。
Cas No.:945714-67-0
Sample solution is provided at 25 µL, 10mM.
FPS-ZM1 is a RAGE-specific inhibitor, with a Ki value of 25nM[1]. FPS-ZM1 has been widely used in the research for improving the inflammatory response[2].
In vitro, FPS-ZM1 treatment (100nM; 1h) significantly inhibited the overexpression of RAGE induced by advanced glycation end product (AGE), RAGE-dependent microglial activation, nuclear translocation of nuclear factor κB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor -α (TNF-α) and interleukin-1 β (IL-1β) in rat primary microglia[3]. Pretreated with 20μM FPS-ZM1 for 2 hours inhibited the expression of pro-inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV-2 cells[4].
In vivo, FPS-ZM1 treatment (1 mg/kg/day; i.p.) for 4 consecutive weeks reduced the production of amyloid-β (Aβ)1-40 and Aβ1-42 in Wistar rats and inhibited the increase of AGE-mediated Aβ metabolism-related proteins in the hippocampus[5]. FPS-ZM1 was administered orally at a dose of 2mg/kg/day for 2 months, reduced the levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLD), α -glutathione S-transferase (α-GST), alkaline phosphatase (ALP) and γ -glutamyl transpeptidase (GGT) in diabetic mice[6]. Intraperitoneal injection of FPS-ZM1 (3mg/kg/day) for 4 consecutive weeks can reduce lipid deposition in hepatocytes and lower the levels of mature SBP-1C, p-p65 nfκb and p-p38 MAPK in liver tissues in KK-Ay mice[7].
References:
[1]Zhou W, Hu W. Anti-neuroinflammatory agents for the treatment of Alzheimer’s disease[J]. Future Medicinal Chemistry, 2013, 5(13): 1559-1571.
[2] Shen L, Zhang T, Yang Y, et al. FPS-ZM1 alleviates neuroinflammation in focal cerebral ischemia rats via blocking ligand/RAGE/DIAPH1 pathway[J]. ACS chemical neuroscience, 2020, 12(1): 63-78.
[3] Shen C, Ma Y, Zeng Z, et al. RAGE-specific inhibitor FPS-ZM1 attenuates AGEs-induced neuroinflammation and oxidative stress in rat primary microglia[J]. Neurochemical research, 2017, 42: 2902-2911.
[4]Wang L, Zhao D, Wang H, et al. FPS-ZM1 inhibits LPS-induced microglial inflammation by suppressing JAK/STAT signaling pathway[J]. International immunopharmacology, 2021, 100: 108117.
[5] Hong Y, Shen C, Yin Q, et al. Effects of RAGE-specific inhibitor FPS-ZM1 on amyloid-β metabolism and AGEs-induced inflammation and oxidative stress in rat hippocampus[J]. Neurochemical research, 2016, 41: 1192-1199.
[6] Aslani S, Bahrambeigi S, Sanajou D. FPS-ZM1 Alleviates Circulating Indices of Liver Injury in Diet-Induced Type 2 Diabetic Mice[J]. Acta Medica Iranica, 2022: 40-45.
[7] Zhang M, Zhao W, Zhang Z, et al. FPS-ZM1 attenuates the deposition of lipid in the liver of diabetic mice by sterol regulatory element binding protein-1c[J]. BMC Endocrine Disorders, 2024, 24(1): 164.
FPS-ZM1是一种特异性RAGE抑制剂，Ki值为25nM[1]。FPS-ZM1被广泛应用于改善炎症反应的研究中[2]。
在体外，100nM浓度的FPS-ZM1处理1小时能显著抑制大鼠原代小胶质细胞中由晚期糖基化终末产物（AGE）诱导的RAGE过表达，阻断RAGE依赖性小胶质细胞活化，抑制核因子κB p65（NF-κB p65）的核转位，并降低肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）等下游炎症介质的表达[3]。使用20μM浓度的FPS-ZM1预处理BV-2细胞2小时，可抑制脂多糖（LPS）诱导的促炎介质和细胞因子的表达[4]。
在体内，连续4周FPS-ZM1处理（1mg/kg/day；i.p.）能降低Wistar大鼠脑内淀粉样蛋白Aβ1-40和Aβ1-42的产生，并抑制海马区AGE介导的Aβ代谢相关蛋白升高[5]。FPS-ZM1经口服给药（2mg/kg/day）两个月后，糖尿病小鼠中的血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、谷氨酸脱氢酶（GLD）、α-谷胱甘肽S-转移酶（α-GST）、碱性磷酸酶（ALP）和γ-谷氨酰转肽酶（GGT）水平均显著降低[6]。连续4周腹腔注射3mg/kg/day剂量的FPS-ZM1后，KK-Ay小鼠中的肝细胞脂质沉积减少，肝组织中成熟SBP-1C、p-p65 NF-κB和p-p38 MAPK水平下降[7]。
| Cell experiment [1]: | |
Cell lines | BV-2 cells |
Preparation Method | BV-2 cells were cultured in Dulbecco’s modified Eagle’s medium with 10% heat-inactivated fetal bovine serum, 100U/mL penicillin and 100μg/mL streptomycin. The culture temperature was 37℃ and the humidity was 5% CO2. BV-2 cells were seeded in 96-well plates at a density of 2×104cells/mL and cultured for 24 hours. Cells were pretreated with FPS-ZM1 (5, 10, and 20μM) for 2 hours and then treated with LPS (100ng/mL) for 24 hours. After treatment, add 10μL of 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) solution (5mg/mL) to each well and incubate at 37℃ for 3 hours. The formazan was dissolved in 100μL DMSO, and the absorbance at 490nm was recorded using an microplate reader. Determine the levels of inflammatory cytokines IL-6 and TNF-α in the culture medium in accordance with the manufacturer's instructions. |
Reaction Conditions | 5, 10, and 20μM; 2h |
Applications | FPS-ZM1 inhibited the expression of pro-inflammatory mediators and cytokines induced by LPS in a concentration-dependent manner without affecting cell viability. |
| Animal experiment [2]: | |
Animal models | KK-Ay mice |
Preparation Method | Eight KK-Ay mice were fed with the dedicated feed for 8 weeks (15 weeks of age) to establish a mouse model of diabetes mellitus complicated with nonalcoholic fatty liver disease (NAFLD). Eight KK-Ay mice, after being fed a specific diet for 8 weeks, were then fed a specific diet and FPS-ZM1 (3mg/kg/day, i.p.) for 4 weeks. After the experiment was completed, the mice were anesthetized with 50mg/kg pentobarbital sodium. Blood samples are collected through cardiac puncture. All the mice were sacrificed by cervical dislocation. The liver tissues were removed and carefully washed. Subsequently, the tissues were fixed with 4% paraformaldehyde or frozen and stored at -80°C. According to the instructions of the kit, AGEs in plasma were determined by ELISA. Add 50μL of the sample or standard solution to each well of the microplate. Then add 50μL of test reagent A and incubate at 37℃ for 1 hour. After washing three times, add test reagent B and incubate at 37℃ for 30 minutes. After washing 5 times, add 90μL of the substrate. Incubate at 37℃ for 10 minutes and add 50μL of stop solution. Finally, place the microplate into the ELISA reader and read the optical density (OD) value at a wavelength of 450nm. Based on the OD values of standard solution solutions of different concentrations, a standard curve was plotted, and the concentration of AGEs in the sample was calculated through the OD values. |
Dosage form | 3mg/kg/day for 4 week; i.p. |
Applications | FPS-ZM1 treatment significantly reduced lipid deposition in hepatocytes and lowered the levels of mature SBP-1C, p-p65 nfκb and p-p38 MAPK in liver tissues of mice. |
References: | |
| 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 |
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| 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 |
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