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吉非罗齐

吉非罗齐用途

Gemfibrozil 是一种 PPAR-α 激活剂,为一种降脂药；Gemfibrozil 同时是 P450 的非选择性抑制剂,对 CYP2C9,2C19,2C8 和 1A2 的 Ki 值分别为 5.8,24,69 和 82 μM。

吉非罗齐名称

[ CAS 号 ]:
25812-30-0

[ 中文名 ]:
吉非罗齐

[ 英文名 ]:
Gemfibrozil

[中文别名 ]:

[英文别名 ]:

GEMFIBROZIL,USP
2,2-Dimethyl-5-(2,5-dimethylphenoxy)valeric Acid
Genlip
5-(2,5-Dimethylphenoxy)-2,2-dimethylpentanoic acid
EINECS 247-280-2
lopid
CI-7
gevilon
Lipttr
ci-719

吉非罗齐生物活性

[ 描述 ]:

Gemfibrozil 是一种 PPAR-α 激活剂,为一种降脂药；Gemfibrozil 同时是 P450 的非选择性抑制剂,对 CYP2C9,2C19,2C8 和 1A2 的 Ki 值分别为 5.8,24,69 和 82 μM。

[ 相关类别 ]:

信号通路 >> 代谢酶/蛋白酶 >> 细胞色素P450

研究领域 >> 心血管疾病

研究领域 >> 代谢疾病

[ 靶点 ]

PPAR-α

CYP2C9:5.8 μM (Ki)

CYP2C19:24 μM (Ki)

CYP2C8:69 μM (Ki)

CYP1A2:82 μM (Ki)

[体外研究]

吉非罗齐是PPAR-α的活化剂,用作降脂药物[1];也是几种P450同种型的非选择性抑制剂,CYP2C9,2C19,2C8和1A2的Ki值分别为5.8,24,69和82μM[3]。吉非罗齐(100,150,200μM)在人U373MG星形胶质细胞中以浓度依赖性方式抑制细胞因子诱导的NO产生,并且这种效应不是由于iNOS mRNA稳定性的任何变化。吉非罗齐(50,100,200μM)抑制细胞因子刺激的人U373MG星形胶质细胞中的人iNOS启动子衍生的荧光素酶活性。此外,吉非罗齐(50,100,150和200μM)对细胞活力没有影响[1]。吉非罗齐显着抑制M-23和M-1的形成(由CYP2C8和CYP3A4催化),在人肝微粒体中Ki(IC50)值分别为69μM(95μM)和273μM(>250μM)。吉非罗齐(0-250μM)剂量依赖性地抑制重组CYP2C8中M-23(IC50,68μM)和M-1(IC50,78μM)的形成,但对重组CYP3A4中这些代谢物的形成没有显着影响。 [3]。

[体内研究]

在脊髓损伤(SCI)前3天开始使用吉非罗齐(62mg/kg /天,口服)治疗引起的运动功能降低,并诱导小鼠损伤后白质减少的趋势。吉非罗齐(62mg/kg /天,po)降低巨噬细胞免疫反应性,但增加T细胞浸润到备用组织中[2]。

[激酶实验]

测定CYP3A4（睾酮6β-羟基化）和CYP2C8（紫杉醇6α-羟基化）的活性。使用的标记物底物浓度，25μM睾酮和1至5μM紫杉醇，与反应的Km值相当或在其附近。将Gemfibrozil与标记物底物和NADPH（1 mM）在37°C共孵育15分钟，然后用人肝微粒体（0.1 mg / mL）开始反应，或者在添加人肝微粒体和NADPH前预孵育15分钟标记基质[3]。

[细胞实验]

简言之，使400μL培养上清液与200μLGriess试剂反应，并在室温下温育15分钟。在570nm处通过分光光度法测量测定样品的光密度。新鲜培养基在所有实验中都是空白。亚硝酸盐浓度由测定中NaNO2反应得到的标准曲线计算[1]。

[动物实验]

在SCI之前3天开始给予小鼠载体或吉非贝齐，以确保在损伤时药物可用性（n = 5-6 /组）。通过将药物溶解在乙醇（0.25％w / w的吉非贝齐）中并涂覆食物颗粒使得每只动物接受约62mg / kg /天的药物来口服递送药物;对照组的食物用乙醇处理。在将食物给予动物之前，允许每组的乙醇完全蒸发。此外，动物在受伤后1小时接受腹腔注射载体或吉非贝齐（500μg溶于200μLPBS），然后继续在其食物中接受药物直至研究结束（伤后28天） [2]。

[参考文献]

[1]. Pahan K, et al. Gemfibrozil, a lipid-lowering drug, inhibits the induction of nitric-oxide synthase in human astrocytes. J Biol Chem. 2002 Nov 29;277(48):45984-91. Epub 2002 Sep 18.

[2]. Almad A, et al. The PPAR alpha agonist gemfibrozil is an ineffective treatment for spinal cord injured mice. Exp Neurol. 2011 Dec;232(2):309-17.

[3]. Wang JS, et al. Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos. 2002 Dec;30(12):1352-6.

[相关活性小分子]

吉非罗齐物理化学性质

[ 密度 ]:
1.0±0.1 g/cm3

[ 沸点 ]:
394.7±30.0 °C at 760 mmHg

[ 熔点 ]:
61-63°C

[ 分子式 ]:
C₁₅H₂₂O₃

[ 分子量 ]:
250.333

[ 闪点 ]:
141.6±18.1 °C

[ 精确质量 ]:
250.156891

[ PSA ]:
46.53000

[ LogP ]:
4.39

[ 外观性状 ]:
白色结晶粉末

[ 蒸汽压 ]:
0.0±1.0 mmHg at 25°C

[ 折射率 ]:
1.512

[ 储存条件 ]:
-20°C Freezer

[ 水溶解性 ]:
可溶于：甲醇

吉非罗齐MSDS

详细MSDS(安全技术说明书)

吉非罗齐毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YV7120000

CHEMICAL NAME :: Valeric acid, 2,2-dimethyl-5-(2,5-xylyloxy)-

CAS REGISTRY NUMBER :: 25812-30-0

LAST UPDATED :: 199801

DATA ITEMS CITED :: 19

MOLECULAR FORMULA :: C15-H22-O3

MOLECULAR WEIGHT :: 250.37

WISWESSER LINE NOTATION :: QVX1&1&3OR B1 E1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 18 gm/kg/3Y-I

TOXIC EFFECTS :: Behavioral - muscle weakness Kidney, Ureter, Bladder - changes in tubules (including acute renal failure, acute tubular necrosis)

REFERENCE :: AIMDAP Archives of Internal Medicine. (AMA, 535 N. Dearborn St., Chicago, IL 60610) V.1- 1908- Volume(issue)/page/year: 151,1873,1991

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1414 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression

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: 25,645,1997

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 445 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity)

REFERENCE :: TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (6),38,1995

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2218 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity)

REFERENCE :: TOVEFN Toksikologicheskii Vestnik. (18-20 Vadkovskii per. Moscow, 101479, Russia) History Unknown Volume(issue)/page/year: (6),38,1995

TYPE OF TEST :: LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Gastrointestinal - nausea or vomiting Gastrointestinal - other changes

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: 25,699,1997 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 2864 mg/kg/13D-C

TOXIC EFFECTS :: Liver - changes in liver weight

REFERENCE :: JJATDK JAT, Journal of Applied Toxicology. (John Wiley & Sons Ltd., Baffins Lane, Chichester, W. Sussex PO19 1UD, UK) V.1- 1981- Volume(issue)/page/year: 17,47,1996

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 13650 mg/kg/13W-C

TOXIC EFFECTS :: Liver - other changes Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in bone marrow (not otherwise specified)

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: 25,653,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 27300 mg/kg/13-I

TOXIC EFFECTS :: Liver - changes in liver weight Blood - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

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: 25,703,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 54600 mg/kg/1Y-I

TOXIC EFFECTS :: Liver - other changes Blood - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

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: 25,703,1997

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Bird - quail

DOSE/DURATION :: 5600 mg/kg/4W-I

TOXIC EFFECTS :: Endocrine - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)

REFERENCE :: IJEBA6 Indian Journal of Experimental Biology. (Publications & Information Directorate, CSIR, Hillside Rd., New Delhi 110 012, India) V.1- 1963- Volume(issue)/page/year: 34,987,1996 ** TUMORIGENIC DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 218 gm/kg/2Y-C

TOXIC EFFECTS :: Tumorigenic - Carcinogenic by RTECS criteria Liver - tumors Reproductive - Tumorigenic effects - testicular tumors

REFERENCE :: JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 67,1105,1981

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 16 gm/kg/78W-C

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

REFERENCE :: JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 67,1105,1981

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 22 gm/kg/2Y-C

TOXIC EFFECTS :: Tumorigenic - neoplastic by RTECS criteria Endocrine - tumors Reproductive - Tumorigenic effects - testicular tumors

REFERENCE :: JJIND8 JNCI, Journal of the National Cancer Institute. (Washington, DC) V.61-79, 1978-87. For publisher information, see JNCIEQ. Volume(issue)/page/year: 67,1105,1981 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2648 mg/kg

SEX/DURATION :: female 15-22 day(s) after conception

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 8,454,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 18910 mg/kg

SEX/DURATION :: male 61 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: FAATDF Fundamental and Applied Toxicology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1981- Volume(issue)/page/year: 8,454,1987 *** REVIEWS *** IARC Cancer Review:Animal Limited Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,427,1996 IARC Cancer Review:Human Inadequate Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,427,1996 IARC Cancer Review:Group 3 IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 66,427,1996

吉非罗齐安全信息

[ 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,Xi

[ 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 ]:
YV7120000

[ 海关编码 ]:
2918990090

吉非罗齐合成路线

详细合成路线

吉非罗齐上下游产品

吉非罗齐上游产品

吉非罗齐下游产品

吉非罗齐制备

1.由2,5-二甲基苯酚和溴氯丙烷反应生成1-（2,5-二甲基苯氧基）-3-氯丙烷。反应在甲苯中进行,加入新洁而灭回流反应5h。

2.由异丁酸钠和异殊途同归胺锂反应生成锂代异丁酸。

吉非罗齐海关

[ 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%

吉非罗齐文献

An orphan esterase ABHD10 modulates probenecid acyl glucuronidation in human liver.

Drug Metab. Dispos. 42(12) , 2109-16, (2014)

Probenecid, a widely used uricosuric agent, is mainly metabolized to probenecid acyl glucuronide (PRAG), which is considered a causal substance of severe allergic or anaphylactoid reactions. PRAG can ...

Analytical and biological characterization of halogenated gemfibrozil produced through chlorination of wastewater.

Environ. Sci. Technol. 46(10) , 5583-9, (2012)

The cholesterol-lowering pharmaceutical gemfibrozil is a relevant environmental contaminant because of its frequency of detection in U.S. wastewaters at concentrations which have been shown to disrupt...

Monitoring and removal of residual phthalate esters and pharmaceuticals in the drinking water of Kaohsiung City, Taiwan.

J. Hazard. Mater. 277 , 53-61, (2014)

This study monitored the occurrence and removal efficiencies of 8 phthalate esters (PAEs) and 13 pharmaceuticals present in the drinking water of Kaohsiung City, Taiwan. The simultaneous electrocoagul...

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