米诺环素

米诺环素用途

米诺环素是一种口服活性、强效和BBB渗透的半合成四环素抗生素。米诺环素是一种缺氧诱导因子(HIF)-1α抑制剂。米诺环素具有抗癌、抗炎和谷氨酸拮抗作用。米诺环素可减少谷氨酸神经传递,并具有神经保护和抗抑郁作用。米诺环素通过与细菌核糖体的30S亚单位结合抑制细菌蛋白质合成,从而产生抑菌作用[1][2][3][4][5][6][7]。

米诺环素名称

[ CAS 号 ]:
10118-90-8

[ 中文名 ]:
米诺环素

[ 英文名 ]:
Minocycline

[中文别名 ]:

[英文别名 ]:

Minocyclin
Minocin
7-dimethylamino-6-demethyl-6-deoxytetracycline
Minocyclinum
Apo-Minocycline
Minocycline
Arestin
7-(N,N-dimethylamino)sancycline
Aknemin
Minocyclinum [INN-Latin]

米诺环素生物活性

[ 描述 ]:

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钙通道

信号通路 >> 细胞凋亡 >> 细胞凋亡

研究领域 >> 癌症

研究领域 >> 心血管疾病

研究领域 >> 感染

信号通路 >> 细胞凋亡 >> MDM-2/p53

研究领域 >> 炎症/免疫

信号通路 >> 代谢酶/蛋白酶 >> HIF/HIF脯氨酰-羟化酶

研究领域 >> 代谢疾病

研究领域 >> 神经疾病

信号通路 >> 跨膜转运 >> 钾通道

信号通路 >> 抗感染 >> 细菌

[ 靶点 ]

L-type calcium channel

[体外研究]

米诺环素(0-100μM,24-72小时)抑制卵巢癌细胞系(OVCAR-3、SKOV-3和A2780)的增殖和克隆形成活性[3]。米诺环素(0-100μM,24-48小时)通过抑制细胞周期蛋白和抑制DNA掺入来阻止细胞周期[3]。米诺环素(0-100μM,72小时)诱导卵巢癌细胞系中的细胞凋亡[3]。米诺环素显示出直接的神经元保护,这种保护模式可能与线粒体完整性和细胞色素c的保存有关,随后抑制caspase依赖性和caspase非依赖性细胞死亡[2]。米诺环素导致缺氧诱导因子(HIF)-1α的抑制,伴随着p53蛋白水平的上调和AKT/mTOR/p70S6K/4E-BP1途径的失活[6]。细胞增殖试验[3]细胞系：人卵巢癌细胞系(OVCAR-3、SKOV-3和A2780)和原代细胞(HEK-293、HMEC、HUVEC、ATCC)浓度：0、1、10、50和100μM孵育时间：24、48或

[体内研究]

米诺环素(0-30mg/kg,口服,每日4周)抑制雌性裸鼠OVCAR-3肿瘤生长[3]。在大剂量腹腔注射时,米诺环素(IP)是脑缺血动物模型中的有效神经保护剂[1]。米诺环素(0-40mg/kg,IP,一次)可显著减轻甲基苯丙胺诱导的小鼠过度运动和行为敏化[2]。米诺环素(3和10 mg/kg,静脉注射一次)可有效减少暂时性大脑中动脉闭塞模型(TMCAO)中的梗死面积[1]。二甲胺四环素(3-10 mg/kg,静脉注射一次)的血清水平(3 mg/kg)与标准200 mg剂量后的人体水平相似[1]。米诺环素减轻大鼠缺血诱发的室性心律失常。这种效应可能与PI3K/Akt信号通路、线粒体KATP通道和L型Ca2+通道的激活有关[7]。动物模型：雌性裸鼠(6周龄,每组9只,将OVCAR-3细胞经皮下注射至左侧腹壁

[参考文献]

[1]. Xu L, et al. Low dose intravenous minocycline is neuroprotective after middle cerebral artery occlusion-reperfusion in rats. BMC Neurol. 2004 Apr 26;4:7.

[2]. Zhang L, et al. Protective effects of minocycline on behavioral changes and neurotoxicity in mice after administration of methamphetamine. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Dec 30;30(8):1381-93.

[3]. Pourgholami MH, et al. Minocycline inhibits growth of epithelial ovarian cancer. Gynecol Oncol. 2012 May;125(2):433-40.

[4]. Molina-Hernández M, et al. Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):380-6.

[5]. Ritchie DJ, et al. A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections. Clin Infect Dis. 2014 Dec 1;59 Suppl 6:S374-80.

[6]. Ataie-Kachoie P, et al. Minocycline attenuates hypoxia-inducible factor-1α expression correlated with modulation of p53 and AKT/mTOR/p70S6K/4E-BP1 pathway in ovarian cancer: in vitro and in vivo studies. Am J Cancer Res. 2015 Jan 15;5(2):575-88.

[7]. Hu X, Wu B, Wang X, Xu C, He B, Cui B, Lu Z, Jiang H. Minocycline attenuates ischemia-induced ventricular arrhythmias in rats. Eur J Pharmacol. 2011 Mar 11;654(3):274-9.

米诺环素物理化学性质

[ 密度 ]:
1.6±0.1 g/cm3

[ 沸点 ]:
803.3±65.0 °C at 760 mmHg

[ 分子式 ]:
C₂₃H₂₇N₃O₇

[ 分子量 ]:
457.476

[ 闪点 ]:
439.6±34.3 °C

[ 精确质量 ]:
457.184906

[ PSA ]:
164.63000

[ LogP ]:
-0.65

[ 外观性状 ]:
亮黄色-橙色非晶形的固体

[ 蒸汽压 ]:
0.0±3.0 mmHg at 25°C

[ 折射率 ]:
1.718

米诺环素毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QI7630000

CHEMICAL NAME :: 2-Naphthacenecarboxamide, 4,7-bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro -3,10,12,12a- tetrahydroxy-1,11-dioxo-

CAS REGISTRY NUMBER :: 10118-90-8

LAST UPDATED :: 199712

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C23-H27-N3-O7

MOLECULAR WEIGHT :: 457.53

WISWESSER LINE NOTATION :: L E6 C666 BV FV CU GUTTT&J DQ EQ GMVH HQ IN1&1 ON1&1 RQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 28 mg/kg/2W-I

TOXIC EFFECTS :: Brain and Coverings - changes in circulation (hemorrhage, thrombosis, etc.) Sense Organs and Special Senses (Eye) - visual field changes Behavioral - headache

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - man

DOSE/DURATION :: 343 mg/kg/17W-I

TOXIC EFFECTS :: Liver - hepatitis (hepatocellular necrosis), diffuse Liver - liver function tests impaired Blood - eosinophilia

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 112 mg/kg/4W-I

TOXIC EFFECTS :: Liver - liver function tests impaired Skin and Appendages - dermatitis, other (after systemic exposure) Nutritional and Gross Metabolic - body temperature increase

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 100 mg/kg

TOXIC EFFECTS :: Kidney, Ureter, Bladder - interstitial nephritis Kidney, Ureter, Bladder - proteinuria Kidney, Ureter, Bladder - hematuria

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 1204 mg/kg/86W-I

TOXIC EFFECTS :: Musculoskeletal - joints

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Human - woman

DOSE/DURATION :: 730 mg/kg/1Y-I

TOXIC EFFECTS :: Behavioral - anorexia (human) Gastrointestinal - nausea or vomiting Liver - liver function tests impaired

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 3100 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 :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 310 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 :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 140 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 :: Intracerebral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 38 mg/kg

TOXIC EFFECTS :: Behavioral - hallucinations, distorted perceptions Behavioral - excitement Musculoskeletal - changes in teeth and supporting structures

MUTATION DATA

TYPE OF TEST :: DNA inhibition

TEST SYSTEM :: Human Lymphocyte

DOSE/DURATION :: 3750 ug/L

REFERENCE :: BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year: 16,127,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3732 No. of Facilities: 13 (estimated) No. of Industries: 1 No. of Occupations: 2 No. of Employees: 7704 (estimated) No. of Female Employees: 7190 (estimated)

米诺环素合成路线

详细合成路线

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米诺环素相关知识

多西环素和米诺环素的区别是什么？

2022-04-17 16:37:01

四环素类抗菌药物属于广谱抑菌性抗生素，通过与细菌核糖体30S亚基结合，抑制蛋白质合成发挥抗菌作用。目前，临床常用的四环素类抗生素为多西环素和米诺环素。多西环素和米诺环素的区别　　1、米诺环素的抗菌作用最强　　四环素类的抗菌谱包括：G+与G-需氧菌和厌氧菌、立克次体、螺旋体、支原体、...