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CMPF

目录号 : GC40478

CMPF是呋喃脂肪酸的主要代谢物,是一种尿毒症毒素(UT),在生理条件下通过有机阴离子转运蛋白排泄到尿液中。

CMPF Chemical Structure

Cas No.:86879-39-2

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Sample solution is provided at 25 µL, 10mM.

Description

CMPF is the main metabolite of furan fatty acids and is a uremic toxin (UT). Under physiological conditions, it is excreted into urine through organic anion transporters [1]. CMPF has a high albumin-binding property, and increasing the serum concentration of competitive binding molecules (such as free fatty acids like oleic acid) may indirectly affect the binding of CMPF to albumin [2]. CMPF is mainly present in the liver, heart, and brain and participates in metabolic pathways related to cholesterol, fatty acids, and lipid synthesis [3].

In vitro, treatment with CMPF (0-400μM; 0-24h) can dose- and time-dependently reduce the GSH levels and the expression of GPX4, FHC, and FLC in HK-2 and NRK49F kidney cells, and increase ROS levels, lipid peroxidation, and intracellular iron concentration [4]. Treatment with CMPF (87μM; 30min) significantly increased the exposure of phosphatidylserine markers of erythrocytes, the level of icCa2+, and the permeability fragility of erythrocytes [5].

In vivo, treatment with CMPF (6mg/kg/day; 2 weeks; i.p.) increased the fasting blood glucose concentration in a high-fat diet (HFD)-induced obesity mouse model, aggravated glucose tolerance impairment, and simultaneously decreased β-cell function and increased ROS levels [6]. Treatment with CMPF (6mg/kg/day; 7 days; i.p.) enhanced the liver lipid clearance rate in the HFD-induced mouse fatty liver model, while inhibiting liver lipid accumulation and insulin resistance [7].

References:
[1] Luce M, Bouchara A, Pastural M, et al. FP322 THE UREMIC TOXIN 3 CARBOXY 4 METHYL 5 PROPYL 2 FURANPROPANOIC ACID (CMPF): PARADOX OF ANEW NUTRITIONAL MARKER IN HAEMODIALYSIS[J]. Nephrology Dialysis Transplantation, 2018, 33(suppl_1): i139-i139.
[2] Lim, C.-F., Stockigt, J.R., Curtis, A.J., et al. A naturally occuring furan fatty acid enhances drug inhibition of thyroxine binding in serum. Metabolism 42(11), 1468-1474 (1993).
[3] Prentice K J, Wendell S G, Liu Y, et al. CMPF, a metabolite formed upon prescription omega-3-acid ethyl ester supplementation, prevents and reverses steatosis[J]. EBioMedicine, 2018, 27: 200-213.
[4] Park J S, Kim D H, Choi H I, et al. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells[J]. Cell Death & Disease, 2023, 14(2): 78.
[5] Van Spitzenbergen B A K, Andrade G B, Dias E S, et al. The uremic solute 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF) may enhance eryptosis and increase erythrocyte osmotic fragility through potential activation of PIEZO1[J]. Nephrology Dialysis Transplantation, 2025, 40(7): 1342-1349.
[6] Liu Y, Prentice K J, Eversley J A, et al. Rapid elevation in CMPF may act as a tipping point in diabetes development[J]. Cell reports, 2016, 14(12): 2889-2900.
[7] Mohan H, Brandt S L, Kim J H, et al. 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) prevents high fat diet‐induced insulin resistance via maintenance of hepatic lipid homeostasis[J]. Diabetes, Obesity and Metabolism, 2019, 21(1): 61-72.

CMPF是呋喃脂肪酸的主要代谢物,是一种尿毒症毒素(UT),在生理条件下通过有机阴离子转运蛋白排泄到尿液中 [1]。CMPF具有高白蛋白结合特性,增加竞争性结合分子的血清浓度(特别是油酸等游离脂肪酸)的血清浓度可能间接影响CMPF与白蛋白的结合 [2]。CMPF主要存在于肝脏、心脏和大脑中,参与胆固醇、脂肪酸和脂质合成相关的代谢途径 [3]

在体外,CMPF(0-400μM; 0-24h)处理能够以剂量与时间依赖性降低HK-2和NRK49F肾细胞的GSH水平和GPX4、FHC和FLC的表达,并增加ROS水平、脂质过氧化和细胞内铁浓度 [4]。CMPF(87μM; 30min)处理显著增加了红细胞中的红斑病标志物phosphatidylserine暴露、icCa2+的水平和红细胞的渗透脆性 [5]

在体内,CMPF(6mg/kg/day; 2 weeks; i.p.)处理提高了高脂饮食(HFD)诱导的肥胖小鼠模型的空腹血糖浓度,加重了葡萄糖耐量损害,同时β细胞功能下降,ROS水平升高 [6]。CMPF(6mg/kg/day; 7 days; i.p.)治疗增强了HFD诱导的小鼠脂肪肝模型的肝脂清除率,同时抑制了肝脂积累和胰岛素抵抗 [7]

实验参考方法

Cell experiment [1]:

Cell lines

HK-2 and NRK49F cells

Preparation Method

Human renal proximal tubular epithelial cells (HK-2) were cultured in Dulbecco’s modified Eagle’s Medium-F-12 (DMEM-F12) supplemented with 10% fetal bovine serum. Normal rat kidney fibroblasts (NRK-49F) were grown in DMEM medium supplemented with 5% fetal bovine serum, 100U/mL penicillin, and 100μg/mL streptomycin at 37°C under a humidified 5% CO2 atmosphere. Levels of intracellular ROS were assessed using 5,6-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate (CM-H2DCFDA). Cells were pretreated with 1µM Ferritin-1 and 1µg/ml Deferoxamine for 1h, treated with 400µM CMPF and incubated in DMEM-F12 serum-free medium for 6h. Cells were washed twice with Hanks’ balanced salt solution (HBSS) and incubated with HBSS (without phenol red) containing 10μM CM-H2DCFH-DA for 30min at 37°C. Images were immediately acquired by confocal microscopy on a laser-scanning microscope.

Reaction Conditions

400μM; 6h

Applications

CMPF significantly increased the ROS levels in HK-2 and NRK49F kidney cells.
Animal experiment [2]:

Animal models

CD1 mice and Ob/ob mice

Preparation Method

CD1 mice were placed on a HFD with 60% kcal from fat or a matched sucrose chow diet with 10% kcal from fat for 6 weeks. Mice were maintained on their respective diets while injected intraperitoneally once daily for 2 weeks with 6mg/kg CMPF or vehicle. CMPF was prepared by dissolving in 70% ethanol to a stock concentration of 100mM and diluted in sterile saline for injection. Ob/ob mice were maintained on a standard chow diet throughout the 2 weeks of intraperitoneal (i.p.) injection with 6mg/kg CMPF or vehicle. Mice were monitored for body weight weekly. At the end of the injection period, i.p. GTTs were performed on mice fasted for 14h overnight. Mice were anesthetized using isofluorane. Total blood volume was collected from the chest cavity following removal of the heart. Tissues were collected and flash frozen in liquid nitrogen for future analysis or fixed in a 4% formaldehyde solution for histology.

Dosage form

6mg/kg/day; 2 weeks; i.p.

Applications

The CMPF treatment increased the fasting blood glucose concentration in the obese mouse model induced by a high-fat diet, aggravated glucose tolerance impairment, and simultaneously led to a decline in β-cell function and an increase in ROS levels.

References:
[1] Park J S, Kim D H, Choi H I, et al. 3-Carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) induces cell death through ferroptosis and acts as a trigger of apoptosis in kidney cells[J]. Cell Death & Disease, 2023, 14(2): 78.
[2] Liu Y, Prentice K J, Eversley J A, et al. Rapid elevation in CMPF may act as a tipping point in diabetes development[J]. Cell reports, 2016, 14(12): 2889-2900.

化学性质

Cas No. 86879-39-2 SDF
化学名 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid
Canonical SMILES CCCc1oc(CCC(=O)O)c(C(=O)O)c1C
分子式 C12H16O5 分子量 240.3
溶解度 30 mg/ml in DMF, 30 mg/ml in DMSO, 30 mg/ml in Ethanol 储存条件 Store at -20°C
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1 mg 5 mg 10 mg
1 mM 4.1615 mL 20.8073 mL 41.6146 mL
5 mM 832.3 μL 4.1615 mL 8.3229 mL
10 mM 416.1 μL 2.0807 mL 4.1615 mL
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