匹立尼酸

匹立尼酸用途

Pirinixic acid (Wy-14643) 是一种有效的 PPARα 激动剂,对鼠的 PPARα 和 PPARγ 的 EC50 值分别为 0.63 μM, 32 μM,对人的 PPARα,PPARγ 和 PPARδ 的 EC50 值分别为 5.0 μM,60 μM,35 μM。

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匹立尼酸名称

[ CAS 号 ]:
50892-23-4

[ 中文名 ]:
匹立尼酸

[ 英文名 ]:
Wy-14643

[中文别名 ]:

[英文别名 ]:

WY-14643
Wyeth 14643
T6N CNJ BS1VQ DMR B1 C1& FG
pirinixic acid
MFCD00191335
WY14643

匹立尼酸生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 细胞周期/DNA损伤 >> PPAR

研究领域 >> 炎症/免疫

研究领域 >> 代谢疾病

[ 靶点 ]

PPARα:0.63 μM (EC50)

PPARγ:32 μM (EC50)

[体外研究]

Pirinixic acid(Wy-14643)是PPARα的激动剂,对于小鼠PPARα和PPARγ,EC50为0.63μM,32μM,对于人PPARα,PPARγ和PPARδ分别为5.0μM,60μM,35μM[1]。 Pirinixic酸(Wy-14643;0,10,100μM)增强滑膜成纤维细胞中PPAR-α的蛋白质表达。 Pirinixic acid(0,10,100μM)显示出对LPS刺激的滑膜成纤维细胞中NO和PGE 2产生的抑制作用。 Pirinixic acid还有效下调滑膜成纤维细胞中炎症介质如VCAM-1,ICAM-1,ET-1和TF的表达,阻断滑膜成纤维细胞中LPS诱导的NF-κB活化,IkB磷酸化和NF-κB核转位,但Pirinixic酸对PPAR-α沉默细胞没有影响[2]。

[体内研究]

Pirinixic酸(Wy-14643; 10mg/kg,iv)降低肥胖大鼠的肝损伤和脂质过氧化(MDA)水平。 Pirinixic酸还在Sham和缺血再灌注(IR)组中引起SIRT1活性增加,但对SIRT3蛋白表达没有影响。 Pirinixic酸增强NAD +和ATP水平,并预防大鼠内质网应激(ERS)[3]。

[细胞实验]

在存在或不存在Pirinixic酸的情况下，用LPS（100μg/ mL）处理滑膜成纤维细胞。 PPAR-αsiRNA转染的细胞也用LPS（100μg/ mL）和Pirinixic酸处理。刺激后，使用Griess试剂测定NO的产生。简而言之，将300μL上清液与100μLGriess试剂和2.6mL去离子水混合。将混合物在室温下温育30分钟，并测量548nm处的吸光度。从标准曲线[2]计算上清液中NO的浓度。

[动物实验]

在存在或不存在Wy-14643的情况下，用LPS（100μg/ mL）处理滑膜成纤维细胞。 PPAR-αsiRNA转染的细胞也用LPS（100μg/ mL）和Wy-14643处理。刺激后，使用Griess试剂测定NO的产生。简而言之，将300μL上清液与100μLGriess试剂和2.6mL去离子水混合。将混合物在室温下温育30分钟，并测量548nm处的吸光度。从标准曲线[2]计算上清液中NO的浓度。

[参考文献]

[1]. Willson TM, et al. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000 Feb 24;43(4):527-50.

[2]. Huang D, et al. PPAR-α Agonist WY-14643 Inhibits LPS-Induced Inflammation in Synovial Fibroblasts via NF-kB Pathway. J Mol Neurosci. 2016 Aug;59(4):544-53.

[3]. Pantazi E, et al. PPARα Agonist WY-14643 Induces SIRT1 Activity in Rat Fatty Liver Ischemia-Reperfusion Injury. Biomed Res Int. 2015;2015:894679.

[相关活性小分子]

匹立尼酸物理化学性质

[ 密度 ]:
1.4±0.1 g/cm3

[ 沸点 ]:
514.4±50.0 °C at 760 mmHg

[ 熔点 ]:
155°C

[ 分子式 ]:
C₁₄H₁₄ClN₃O₂S

[ 分子量 ]:
323.798

[ 闪点 ]:
264.9±30.1 °C

[ 精确质量 ]:
323.049530

[ PSA ]:
100.41000

[ LogP ]:
4.92

[ 外观性状 ]:
固体;White to Light yellow powder to crystal

[ 蒸汽压 ]:
0.0±1.4 mmHg at 25°C

[ 折射率 ]:
1.658

[ 储存条件 ]:
Store at RT

匹立尼酸MSDS

详细MSDS(安全技术说明书)

匹立尼酸毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: AG2915000

CHEMICAL NAME :: Acetic acid, ((4-chloro-6-(2,3-xylidino)-2-pyrimidinyl)thio)-

CAS REGISTRY NUMBER :: 50892-23-4

BEILSTEIN REFERENCE NO. :: 0759945

LAST UPDATED :: 199806

DATA ITEMS CITED :: 23

MOLECULAR FORMULA :: C14-H14-Cl-N3-O2-S

MOLECULAR WEIGHT :: 323.82

WISWESSER LINE NOTATION :: T6N CNJ BS1VQ DG FMR B1 C1

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 :: 1050 mg/kg

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

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1600 mg/kg

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

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 330 mg/kg/8W-C

TOXIC EFFECTS :: Liver - changes in liver weight Nutritional and Gross Metabolic - weight loss or decreased weight gain Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 126 mg/kg/21D-C

TOXIC EFFECTS :: Liver - changes in liver weight Related to Chronic Data - changes in prostate weight Related to Chronic Data - changes in testicular weight

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1092 mg/kg/26W-C

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of endocrine pancreas Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - hepatic microsomal mixed oxidase (dealkylation, hydroxylation, etc.)

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1545 mg/kg/2Y-C

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - changes in platelet count Related to Chronic Data - death

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 22 gm/kg/1Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 37 gm/kg/62W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 46 gm/kg/65W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 27 gm/kg/64W-C

TOXIC EFFECTS :: Tumorigenic - equivocal tumorigenic agent by RTECS criteria Liver - tumors

TYPE OF TEST :: TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 29 gm/kg/69W-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors

TYPE OF TEST :: Morphological transformation

TYPE OF TEST :: Unscheduled DNA synthesis

MUTATION DATA

TYPE OF TEST :: Morphological transformation

TEST SYSTEM :: Rodent - hamster Embryo

DOSE/DURATION :: 85 mg/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 356,85,1996

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匹立尼酸安全信息

[ 符号 ]:

GHS07, GHS08

[ 信号词 ]:
Danger

[ 危害声明 ]:
H302-H315-H319-H335-H350

[ 警示性声明 ]:
P201-P261-P305 + P351 + P338-P308 + P313

[ 个人防护装备 ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
T

[ 风险声明 (欧洲) ]:
45-22-36/37/38

[ 安全声明 (欧洲) ]:
S26;S45;S53;S36/S37/S39

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

[ WGK德国 ]:
3

[ RTECS号 ]:
AG2915000

[ 海关编码 ]:
2933599090

匹立尼酸合成路线

详细合成路线

匹立尼酸上下游产品

匹立尼酸上游产品

匹立尼酸下游产品

匹立尼酸海关

[ 海关编码 ]: 2933599090

[ 中文概述 ]:
2933599090. 其他结构上有嘧啶环的化合物(包括其他结构上有哌嗪环的化合物. 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 ]:
2933599090. other compounds containing a pyrimidine ring (whether or not hydrogenated) or piperazine ring in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

匹立尼酸文献

Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol mediated liver fibrosis in mice.

Lipids Health Dis. 12 , 11, (2013)

Peroxisome proliferator activated receptor alpha (PPARα) ameliorates ethanol induced hepatic steatohepatitis. However, its role in alcoholic liver fibrosis has not been fully clarified. The aim of thi...

Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling.

J. Clin. Invest. 123(3) , 1229-40, (2013)

Exogenous dietary fat can induce obesity and promote diabetes, but endogenous fat production is not thought to affect skeletal muscle insulin resistance, an antecedent of metabolic disease. Unexpected...

Genetic ablation of solute carrier family 7a3a leads to hepatic steatosis in zebrafish during fasting.

Hepatology 60(6) , 1929-41, (2014)

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder caused by abnormal lipid metabolisms, such as reduced hepatic fatty acid oxidation (FAO), but intracellular control o...

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