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吡非尼酮

吡非尼酮用途

Pirfenidone是一种用于治疗特发性肺纤维化的药物。它抑制FGFR,EGFR,PDGFR,TGF-β,从而减缓肿瘤细胞增殖。

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吡非尼酮名称

[ CAS 号 ]:
53179-13-8

[ 中文名 ]:
哌非尼酮

[ 英文名 ]:
Pirfenidone

[中文别名 ]:

[英文别名 ]:

TORASEMIDETECHPIRFENIDONE
5-Methyl-1-phenyl-2-(1H)-pyridone
2(1H)-Pyridinone, 5-methyl-1-phenyl-
5-methyl-1-phenyl-2-pyridone
5-Methyl-N-phenyl-2-1H-pyridone
Pirespa
S-7701
amr-69
5-methyl-1-phenyl-1H-pyridin-2-one
5-Methyl-1-phenyl-2(1H)-pyridinone

吡非尼酮生物活性

[ 描述 ]:

Pirfenidone是一种用于治疗特发性肺纤维化的药物。它抑制FGFR,EGFR,PDGFR,TGF-β,从而减缓肿瘤细胞增殖。

[ 相关类别 ]:

信号通路 >> 干细胞及 Wnt 通路 >> TGF-β/Smad蛋白

信号通路 >> TGF-beta/Smad 信号通路 >> TGF-β/Smad蛋白

研究领域 >> 炎症/免疫

[ 靶点 ]

TGF-β2[1]

[体外研究]

吡非尼酮(PFD)降低基质金属蛋白酶(MMP)-11(一种TGF-β靶基因和参与癌发生的弗林蛋白酶底物)的蛋白质水平。这些数据将PFD或PFD相关因子定义为与增强TGF-β活性相关的人类癌症的有希望的药物[1]。在RAW264.7细胞中,小鼠巨噬细胞样细胞系,吡非尼酮通过翻译机制抑制促炎细胞因子TNF-α,其不依赖于MAPK2,p38MAPK和JNK的激活。在小鼠内毒素休克模型中,吡非尼酮有效抑制促炎细胞因子TNF-α,干扰素-γ和白细胞介素-6的产生,但增强了抗炎细胞因子白细胞介素-10的产生[2]。吡非尼酮(PFD)显示其对HLEC增殖的抑制作用。与对照组相比,24小时后0.3mg/mL组的细胞增殖减弱(P = 0.044)。 0.5mg/mL组在24,48和72小时时效果更明显(P <0.05)。在所有时间点,1 mg/mL PFD几乎完全抑制增殖(P <0.01)[3]。

[体内研究]

给予吡非尼酮(300mg/kg /天)4周。当在博来霉素(BLM)处理的小鼠中施用时,吡非尼酮显着减弱评分(P <0.0001)。此外,在肺中定量胶原蛋白含量以评估吡非尼酮的抗纤维化作用。与盐水或吡非尼酮处理的小鼠相比,BLM处理的小鼠肺中的胶原蛋白含量显着增加,并且在BLM处理后第28天,吡非尼酮给药显着减弱了这种增加(P = 0.0012)[4]。

[细胞实验]

将HLEC在96孔板（1×10 4细胞/孔）中接种于α-MEM / 10％FBS / 1％NEAA中24小时，并在无血清培养基中的固定管中培养24小时。然后除去培养基，将细胞浸泡在含有10％FBS和1％NEAA的α-MEM中，补充0,0.01,0.1,0.2,0.3,0.5或1mg / mL吡非尼酮0,4,12， 24,48或72小时。与180μLα-MEM和20μL5mg/ mL MTT在37℃温育4小时后，弃去MTT溶液。通过在轨道振荡器上以200rpm搅拌皿10分钟将甲醇沉淀物溶解在180μLDMSO中。用微量板读数器读取每个孔中490nm处的吸光度。我们通过使用MTT测定法将浓度提高到0.2,0.25,0.3,0.4,0.5和0.6 mg / mL来进一步检查PFD的效果[3]。

[动物实验]

小鼠[4]使用9周龄雌性C57BL / 6小鼠。渗透泵植入后，吡非尼酮口服给药14天。给药量根据体重确定。将动物分成4组（n = 6 /组）：正常对照，BLM，吡非尼酮（300mg / kg /天）和BLM +吡非尼酮。根据其他地方发表的报告选择吡非尼酮剂量。吡非尼酮也在第10天开始以治疗环境施用，以评估药物对BLM模型小鼠的纤维化阶段的影响。

[参考文献]

[1]. Burghardt I, et al. Pirfenidone inhibits TGF-beta expression in malignant glioma cells. Biochem Biophys Res Commun. 2007 Mar 9;354(2):542-7.

[2]. Nakazato H, et al. A novel anti-fibrotic agent pirfenidone suppresses tumor necrosis factor-alpha at the translational level. Eur J Pharmacol. 2002 Jun 20;446(1-3):177-85.

[3]. Yang Y, et al. Inhibition of Pirfenidone on TGF-beta2 induced proliferation, migration and epithlial-mesenchymal transitionof human lens epithelial cells line SRA01/04. PLoS One. 2013;8(2):e56837.

[4]. Inomata M, et al. Pirfenidone inhibits fibrocyte accumulation in the lungs in bleomycin-induced murine pulmonary fibrosis. Respir Res. 2014 Feb 8;15:16.

[5]. Brooks D, et al. Limited fibrosis accompanies triple-negative breast cancer metastasis in multiple model systems and is not a preventive target. Oncotarget. 2018 May 4;9(34):23462-23481.

[相关活性小分子]

吡非尼酮物理化学性质

[ 密度 ]:
1.1±0.1 g/cm3

[ 沸点 ]:
329.1±15.0 °C at 760 mmHg

[ 熔点 ]:
96-97ºC

[ 分子式 ]:
C₁₂H₁₁NO

[ 分子量 ]:
185.222

[ 闪点 ]:
152.7±11.6 °C

[ 精确质量 ]:
185.084061

[ PSA ]:
22.00000

[ LogP ]:
1.82

[ 外观性状 ]:
solid

[ 蒸汽压 ]:
0.0±0.7 mmHg at 25°C

[ 折射率 ]:
1.592

[ 储存条件 ]:
Store at RT

[ 水溶解性 ]:
DMSO: ≥10 mg/mL, soluble

吡非尼酮MSDS

详细MSDS(安全技术说明书)

吡非尼酮毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: UV1148200

CHEMICAL NAME :: 2(1H)-Pyridone, 5-methyl-1-phenyl-

CAS REGISTRY NUMBER :: 53179-13-8

BEILSTEIN REFERENCE NO. :: 1526549

LAST UPDATED :: 199612

DATA ITEMS CITED :: 13

MOLECULAR FORMULA :: C12-H11-N-O

MOLECULAR WEIGHT :: 185.24

WISWESSER LINE NOTATION :: T6NVJ AR& E1

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 :: 1295 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 430 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 580 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4042699

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 420 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #3974281

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 285 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 300 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 200 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 100 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 500 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - cat

DOSE/DURATION :: 40 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 280 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 810 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 460 mg/kg

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

REFERENCE :: EPXXDW European Patent Application. (U.S. Patent and Trademark Office, Foreign Patents, Washington, DC 20231) Volume(issue)/page/year: #383591

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吡非尼酮安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 警示性声明 ]:
P301 + P312 + P330

[ 个人防护装备 ]:
dust mask type N95 (US);Eyeshields;Gloves

[ 危害码 (欧洲) ]:
Xn:Harmful;

[ 风险声明 (欧洲) ]:
R22

[ 安全声明 (欧洲) ]:
S36

[ 危险品运输编码 ]:
NONH for all modes of transport

[ WGK德国 ]:
3

[ RTECS号 ]:
UV1148200

[ 海关编码 ]:
2933399090

吡非尼酮合成路线

详细合成路线

吡非尼酮上下游产品

吡非尼酮上游产品

吡非尼酮下游产品

吡非尼酮海关

[ 海关编码 ]: 2933399090

[ 中文概述 ]:
2933399090. 其他结构含非稠合吡啶环的化合物. 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:20.0%

[ 申报要素 ]: 品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期

[ Summary ]:
2933399090. other compounds containing an unfused pyridine ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

吡非尼酮文献

Lung fibrosis: drug screening and disease biomarker identification with a lung slice culture model and subtracted cDNA Library.

Altern. Lab. Anim. 42(4) , 235-43, (2014)

Pulmonary fibrosis is a progressive and irreversible disorder with no appropriate cure. A practical and effective experimental model that recapitulates the disease will greatly benefit the research co...

A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis.

Am. J. Respir. Cell. Mol. Biol. 52(2) , 217-31, (2015)

The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to h...

Local delivery of biodegradable pirfenidone nanoparticles ameliorates bleomycin-induced pulmonary fibrosis in mice.

Nanotechnology 23(50) , 505101, (2012)

Our purpose was to assess sustained delivery and enhanced efficacy of pirfenidone-loaded nanoparticles after intratracheal instillation.Poly(lactide-co-glycolide) nanoparticles containing pirfenidone ...

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