非诺贝特酸

非诺贝特酸用途

Fenofibric acid 是 fenofibrate 的活性代谢物,为 PPAR 激动剂,对 PPARα,PPARγ 和 PPARδ 的 EC50 值分别为 22.4 µM,1.47 µM 和 1.06 µM；Fenofibric acid 同时可抑制 COX-2 的活性,IC50 值为 48 nM。

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非诺贝特酸名称

[ CAS 号 ]:
42017-89-0

[ 中文名 ]:
非诺贝特酸

[ 英文名 ]:
Fenofibric acid

[中文别名 ]:

[英文别名 ]:

Procetofenic acid
Fibricor
Fenofibric acid
Fenofibrate Related Compound B
Fenofibrate impurity B
EINECS 255-626-9
MFCD00792461

非诺贝特酸生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 代谢疾病

[ 靶点 ]

PPARδ:1.06 μM (EC50)

PPARγ:1.47 μM (EC50)

PPARα:22.4 μM (EC50)

COX-2:48 μM (IC50)

[体外研究]

Fenofibric acid是一种PPAR激活剂,PPARα,PPARγ和PPARδ的EC50分别为22.4μM,1.47μM和1.06μM[1]。非诺贝酸(10,25,50,75和100 nM)剂量依赖性地抑制COX-2酶,IC50为48 nM [2]。非诺贝酸(500 nM)可降低HepG2细胞中AOX1蛋白的丰度[3]。 Fenofibric acid(100μM)可降低JNK1/2,c-Jun和p38 MAPK的磷酸化水平,并可防止活性氧,内质网(ER)应激和血液视网膜屏障(BRB)破坏的积累。 ARPE-19细胞中的高葡萄糖(HG)和缺氧。在HG条件和缺氧条件下,非诺贝酸(100μM)激活ARPE-19细胞中IGF-IR/Akt/ERK1/2介导的存活信号通路[4]。

[体内研究]

Fenofibric acid(1,5,10 mg/kg,po)在由角叉菜胶诱导的急性炎症的Wistar大鼠中显示出抗炎活性[2]。

[细胞实验]

ARPE-19细胞在正常血糖（5.5mM D-葡萄糖）或高血糖（25mM D-葡萄糖）条件下在37℃，5％（v / v）CO 2下培养18天，培养基DMEM / F12补充10％（v / v）胎儿血清（FS）和青霉素/链霉素。使用ARPE-19细胞，每3-4天更换培养基。测试的条件是：（1）将对照细胞维持在5.5mM D-葡萄糖（正常葡萄糖）中18天。（2）在用100μM非诺贝酸处理的5.5mM D-葡萄糖中培养72小时（第16,17和18天;每天施用1次）的细胞。（3）如（1）或（2）中培养的细胞，并在最后6或24小时内进行缺氧（1％氧气）。（4）细胞维持在25mM D-葡萄糖（HG）中18天。（5）在用100μM非诺贝酸处理的25mM D-葡萄糖中培养72小时（第16,17和18天;每天施用1次）的细胞。（6）如（4）或（5）中培养的细胞，在最后6或24小时内进行缺氧（1％氧气）[4]。

[动物实验]

通过将0.1mL在盐水（足底下）中制备的1％角叉菜胶溶液注射到大鼠的右后爪来评估非诺贝特及其活性代谢物fenofibric acid的抗炎活性。将大鼠分成6组，每组6只动物。第一组用作阴性对照，并在蒸馏水中接受1％吐温-80,10mL / kg体重。第2组和第3组接受单剂量非诺贝特和标准药物双氯芬酸10 mg / kg体重，而第4,5和6组分别接受3剂量的Fenofibric acid，分别为1,5和10 mg / kg体重。在通过足底下途径注射0.1mL的1％角叉菜胶之前60分钟使用管饲口服给予所有药物。在诱导炎症后0,1,2和3小时使用体积描记器测量测试组和对照组的水肿体积[2]。

[参考文献]

[1]. Dietz M, et al. Comparative molecular profiling of the PPARα/γ activator aleglitazar: PPAR selectivity, activity and interaction with cofactors. ChemMedChem. 2012 Jun;7(6):1101-11.

[2]. Prasad GS, et al. Anti-inflammatory activity of anti-hyperlipidemic drug, fenofibrate, and its phase-I metabolite fenofibric acid: in silico, in vitro, and in vivo studies. Inflammopharmacology. 2017 Dec 13.

[3]. Neumeier M, et al. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro. Biochem Biophys Res Commun. 2006 Nov 24;350(3):731-5. Epub 2006 Sep 27.

[4]. Miranda S, et al. Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabetic conditions. J Cell Physiol. 2012 Jun;227(6):2352-62.

[相关活性小分子]

非诺贝特酸物理化学性质

[ 密度 ]:
1.3±0.1 g/cm3

[ 沸点 ]:
486.5±35.0 °C at 760 mmHg

[ 熔点 ]:
176--179ºC

[ 分子式 ]:
C₁₇H₁₅ClO₄

[ 分子量 ]:
318.752

[ 闪点 ]:
248.0±25.9 °C

[ 精确质量 ]:
318.065887

[ PSA ]:
63.60000

[ LogP ]:
3.86

[ 外观性状 ]:
白色或近乎于白色结晶粉末

[ 蒸汽压 ]:
0.0±1.3 mmHg at 25°C

[ 折射率 ]:
1.585

[ 储存条件 ]:
-20°C Freezer

非诺贝特酸MSDS

详细MSDS(安全技术说明书)

非诺贝特酸毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UA2453000

CHEMICAL NAME :: Propanoic acid, 2-(4-(4-chlorobenzoyl)phenoxy)-2-methyl-

CAS REGISTRY NUMBER :: 42017-89-0

LAST UPDATED :: 199612

DATA ITEMS CITED :: 4

MOLECULAR FORMULA :: C17-H15-Cl-O4

MOLECULAR WEIGHT :: 318.77

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1242 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,229,1982

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 313 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening

REFERENCE :: YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S873,1995

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1200 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,885,1976

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 500 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 26,885,1976

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非诺贝特酸安全信息

[ 符号 ]:

GHS07, GHS09

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302-H410

[ 警示性声明 ]:
P273-P501

[ 危害码 (欧洲) ]:
Xn,N

[ 风险声明 (欧洲) ]:
R36/37/38

[ 安全声明 (欧洲) ]:
26-36/37/39

[ 危险品运输编码 ]:
UN 3077 9 / PGIII

[ RTECS号 ]:
UA2453000

[ 海关编码 ]:
2918990090

非诺贝特酸合成路线

详细合成路线

非诺贝特酸上下游产品

非诺贝特酸上游产品

非诺贝特酸下游产品

非诺贝特酸海关

[ 海关编码 ]: 2918990090

[ 中文概述 ]:
2918990090. 其他含其他附加含氧基羧酸（包括酸酐、酰卤化物、过氧化物和过氧酸及该税号的衍生物）. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:30.0%

[ 申报要素 ]: 品名, 成分含量, 用途

[ Summary ]:
2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

非诺贝特酸文献

Enzymatic characterization of ELOVL1, a key enzyme in very long-chain fatty acid synthesis.

Biochim. Biophys. Acta 1851(2) , 231-7, (2015)

X-linked adrenoleukodystrophy (X-ALD) is a neurometabolic disease that is caused by mutations in the ABCD1 gene. ABCD1 protein deficiency impairs peroxisomal very long-chain fatty acid (VLCFA) degrada...

The Lidose hard capsule formulation of fenofibrate is suprabioavailable compared to the nanoparticle tablet formulation under high-fat fed conditions.

J. Pharm. Pharm. Sci. 18(1) , 61-7, (2015)

The therapeutic equivalence of multiple registered fenofibrate formulations, several of which are suprabioavailable and therefore marketed at lower dosage strengths than their reference products, is b...

Endoplasmic reticulum stress involved in high-fat diet and palmitic acid-induced vascular damages and fenofibrate intervention.

Biochem. Biophys. Res. Commun. 458(1) , 1-7, (2015)

Fenofibrate (FF) is widely used to lower blood lipids in clinical practice, but whether its protective effect on endothelium-dependent vasodilatation (EDV) in thoracic aorta is related with endoplasmi...

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