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盐酸二甲双胍

盐酸二甲双胍用途

Metformin (hydrochloride) 是FDA批准的用于治疗2型糖尿病的一线药物。 二甲双胍主要是通过对线粒体呼吸链复合物1的轻度和短暂抑制降低肝脏葡萄糖的产生。
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盐酸二甲双胍名称

[ CAS 号 ]:
1115-70-4

[ 中文名 ]:
盐酸二甲双胍

[ 英文名 ]:
Metformin HCl

[中文别名 ]:

[英文别名 ]:

盐酸二甲双胍生物活性

[ 描述 ]:

Metformin (hydrochloride) 是FDA批准的用于治疗2型糖尿病的一线药物。 二甲双胍主要是通过对线粒体呼吸链复合物1的轻度和短暂抑制降低肝脏葡萄糖的产生。

[ 相关类别 ]:

信号通路 >> 表观遗传学 >> AMPK
信号通路 >> PI3K/Akt/mTOR 信号通路 >> AMPK
信号通路 >> 自噬 >> 自噬
信号通路 >> 自噬 >> 自噬
研究领域 >> 癌症

[ 靶点 ]

AMPK

Autophagy

Mitophagy


[体外研究]

二甲双胍以浓度依赖性方式抑制ESC的增殖。 A-ESC的IC50为2.45mM,N-ESC的IC50为7.87mM。二甲双胍对分泌期A-ESC中AMPK信号激活的激活作用显着高于增殖期细胞[3]。二甲双胍(0-500μM)以剂量依赖性方式降低糖原合成,在培养的大鼠肝细胞中IC50值为196.5μM[4]。二甲双胍显示细胞活力和对PC-3细胞的细胞毒性作用,IC50为5 mM [5]。

[体内研究]

单独使用二甲双胍(100 mg/kg,口服)和使用异丙肾上腺素基团的二甲双胍(25,50,100 mg/kg)通过组织病理学分析减轻肌细胞坏死[1]。二甲双胍(> 900mg/kg /天,口服)导致Crl：CD(SD)大鼠的濒死/死亡和临床毒性迹象[2]。

[细胞实验]

将ESC以1×10 3个细胞/孔的浓度接种在96孔板中。附着后，用不同剂量的二甲双胍/化合物C处理细胞0分钟，15分钟，1小时和24小时。如前所述进行MTT测定。简言之，将MTT（5mg / mL）以10μL/孔的体积加入96孔板中，并将板孵育4小时。通过除去含有MTT的培养基终止MTT反应，并且每孔加入100μLDMSO并在室温下在振荡器上孵育10分钟以确保晶体充分溶解。吸光度值在595nm处测量。细胞增殖（对照的百分比）计算如下：吸光度（实验组）/吸光度（对照组）。如下计算细胞增殖抑制（对照的百分比）：100％细胞增殖（对照的百分比）。每个实验一式两份进行并重复六次以评估结果一致性。

[动物实验]

将动物随机分成6组，每组6只大鼠。组1（对照）的大鼠接受皮下注射生理盐水（0.5mL）并在整个实验期间不进行治疗。组2中的大鼠口服给予二甲双胍（100mg / kg;每天两次）2天，并以24小时的间隔皮下注射盐水连续2天。组3（MI对照）的大鼠口服盐水（每天两次）2天，每天皮下注射异丙肾上腺素（100mg / kg）连续2天，间隔24小时。第4组至第6组的大鼠用25,50和100mg / kg的二甲双胍处理。将二甲双胍溶解在盐水中，并以12小时的间隔每天两次以0.25-0.5mL的体积强饲，在异丙肾上腺素注射之前立即开始。

[参考文献]

[1]. Soraya H, et al. Acute treatment with metformin improves cardiac function following isoproterenol induced myocardial infarction in rats. Pharmacol Rep. 2012;64(6):1476-84.

[2]. Quaile MP, et al. Toxicity and toxicokinetics of metformin in rats. Toxicol Appl Pharmacol. 2010 Mar 15;243(3):340-7.

[3]. Xue J, et al. Metformin inhibits growth of eutopic stromal cells from adenomyotic endometrium via AMPK activation and subsequent inhibition of AKT phosphorylation: a possible role in the treatment of adenomyosis. Reproduction. 2013 Aug 21;146(4):397-406.

[4]. Otto M, et al. Metformin inhibits glycogen synthesis and gluconeogenesis in cultured rat hepatocytes. Diabetes Obes Metab. 2003 May;5(3):189-94.

[5]. Avci CB, et al. Therapeutic potential of an anti-diabetic drug, metformin: alteration of miRNA expression in prostate cancer cells. Asian Pac J Cancer Prev. 2013;14(2):765-8.

[6]. Nie L, et al. The Landscape of Histone Modifications in a High-Fat Diet-Induced Obese (DIO) Mouse Model. Mol Cell Proteomics. 2017 Jul;16(7):1324-1334.

[7]. Zhang D, et al. Metformin ameliorates BSCB disruption by inhibiting neutrophil infiltration and MMP-9 expression but not direct TJ proteins expression regulation. J Cell Mol Med. 2017 Jul 12.


[相关活性小分子]

3-甲基腺嘌呤 | 4-(4-氟苯基)-2-(4-甲基亚磺酰基苯基)-5-(4-吡啶基)-1H-咪唑 | U0126-EtOH | Dorsomorphin dihydrochloride | 阿卡地辛 | 布雷菲德菌素A | 坦螺旋霉素 | 白藜芦醇 | 褪黑素 | 姜黄素 | 盐霉素 | 2-乙基-3-甲基戊酰胺 | 槲皮素 | 4-羟基-3-(2'-羟基-1,1'-联苯-4-基)-6-氧代-6,7-二氢噻吩并[2,3-B]吡啶-5-甲腈 | 雷公藤红素; 南蛇藤素

盐酸二甲双胍物理化学性质

[ 沸点 ]:
224.1ºC at 760 mmHg

[ 熔点 ]:
223-226 °C(lit.)

[ 分子式 ]:
C4H12ClN5

[ 分子量 ]:
165.625

[ 闪点 ]:
89.3ºC

[ 精确质量 ]:
165.078125

[ PSA ]:
88.99000

[ LogP ]:
1.05850

[ 外观性状 ]:
结晶固体

[ 蒸汽压 ]:
0.0929mmHg at 25°C

[ 储存条件 ]:
Store at RT

[ 水溶解性 ]:
水溶性：完全溶解；极微溶：乙醇

盐酸二甲双胍MSDS

详细MSDS(安全技术说明书)

盐酸二甲双胍毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :
DU1800000
CHEMICAL NAME :
Biguanide, 1,1-dimethyl-, hydrochloride
CAS REGISTRY NUMBER :
1115-70-4
LAST UPDATED :
199801
DATA ITEMS CITED :
16
MOLECULAR FORMULA :
C4-H11-N5.Cl-H
MOLECULAR WEIGHT :
165.66
WISWESSER LINE NOTATION :
MUYZMYUM&N1&1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
Standard Draize test
ROUTE OF EXPOSURE :
Administration onto the skin
SPECIES OBSERVED :
Rodent - rabbit
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 20,563,1982
TYPE OF TEST :
Standard Draize test
ROUTE OF EXPOSURE :
Administration into the eye
SPECIES OBSERVED :
Rodent - rabbit
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 20,573,1982
TYPE OF TEST :
Rinsed with water
ROUTE OF EXPOSURE :
Administration into the eye
SPECIES OBSERVED :
Rodent - rabbit
REFERENCE :
FCTOD7 Food and Chemical Toxicology. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.20- 1982- Volume(issue)/page/year: 20,573,1982 ** ACUTE TOXICITY DATA **
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
1 gm/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85KYAH "Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals", 11th ed., Rahway, NJ 07065, Merck & Co., Inc. 1989 Volume(issue)/page/year: 11,934,1989
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
300 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85KYAH "Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals", 11th ed., Rahway, NJ 07065, Merck & Co., Inc. 1989 Volume(issue)/page/year: 11,934,1989
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
1450 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,841,1982
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 :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: 6,841,1982
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
225 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1193,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
180 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
CSLNX* U.S. Army Armament Research & Development Command, Chemical Systems Laboratory, NIOSH Exchange Chemicals. (Aberdeen Proving Ground, MD 21010) Volume(issue)/page/year: NX#04012
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rabbit
DOSE/DURATION :
350 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1193,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - rabbit
DOSE/DURATION :
150 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1193,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
500 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1193,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,474,1960
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Subcutaneous
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
150 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,1193,1990
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intramuscular
SPECIES OBSERVED :
Rodent - guinea pig
DOSE/DURATION :
200 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,474,1960 ** OTHER MULTIPLE DOSE TOXICITY DATA **
TYPE OF TEST :
TDLo - Lowest published toxic dose
ROUTE OF EXPOSURE :
Intracerebral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
40 mg/kg/10D-C
TOXIC EFFECTS :
Behavioral - changes in motor activity (specific assay) Vascular - BP lowering not characterized in autonomic section Related to Chronic Data - death
REFERENCE :
PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987- Volume(issue)/page/year: 81,7,1997
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盐酸二甲双胍安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302-H315-H319

[ 警示性声明 ]:
P305 + P351 + P338

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

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
R22;R36/38

[ 安全声明 (欧洲) ]:
S26-S36

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

[ WGK德国 ]:
3

[ RTECS号 ]:
DU1800000

[ 海关编码 ]:
2925290090

盐酸二甲双胍合成路线

详细合成路线

盐酸二甲双胍上下游产品

盐酸二甲双胍上游产品

盐酸二甲双胍下游产品

盐酸二甲双胍制备

由二甲胺成盐后与双氰胺反应而得。

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盐酸二甲双胍海关

[ 海关编码 ]: 2925290090

[ 中文概述 ]:
2925290090 其他亚胺及其衍生物，以及它们的盐。监管条件:无。增值税率:17.0%。退税率:9.0%。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 ]:
2925290090 other imines and their derivatives; salts thereof。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。MFN tariff:6.5%。General tariff:30.0%

盐酸二甲双胍文献

Differential effects of AMPK agonists on cell growth and metabolism.

Oncogene 34 , 3627-39, (2015)

As a sensor of cellular energy status, the AMP-activated protein kinase (AMPK) is believed to act in opposition to the metabolic phenotypes favored by proliferating tumor cells. Consequently, compound...

Fermentation of Green Tea with 2% Aquilariae lignum Increases the Anti-Diabetic Activity of Green Tea Aqueous Extracts in the High Fat-Fed Mouse.

Nutrients 7 , 9046-78, (2015)

Anti-diabetic effects on the metabolomic differences between green tea (GT) and Aquilariae lignum-fermented green tea (fGT) were investigated in the high fat-fed mouse. To prove the differences, hypog...

Phosphorylation of ULK1 by AMPK regulates translocation of ULK1 to mitochondria and mitophagy.

FEBS Lett. 589 , 1847-54, (2015)

UNC-51 like kinase (ULK1) translocates to dysfunctional mitochondria and is involved in mitophagy, but the mechanisms responsible for ULK1 activation and translocation remain unclear. Here, we found t...


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