Bacterial protein synthesis; 30S subunit of the bacterial ribosome; tetracycline antibiotic; hypoxia-inducible factor (HIF)-1α

OVCAR-3、SKOV-3 和 A2780 珍珠棉系的增殖和克隆形成活性受到盐酸米诺环素（0-100 μM，24-72 小时）的抑制 [3]。米诺环素盐酸盐（0-100 μM，24-48 小时）。在示波器中，盐酸米诺环素（0-100 μM，72 小时））会引起细胞周期 [3]。除了抑制 caspase 依赖性和 caspase 非依赖性细胞死亡外，直接神经保护还可能与线粒体异常和细胞色素 c 保护有关 [2]。盐酸米诺环素诱导缺氧诱导因子（HIF）细胞增殖的检测[3]

在雌性裸鼠中，每天一次静脉注射盐酸卵分泌素（0-30 mg/kg），持续四个星期，可抑制 OVCAR-3 肿瘤的生长[3]。在脑损伤动物模型中，盐酸米诺环素 (IP) 是一种强效药物，在腹腔内高剂量给药时表现出神经保护作用 [1]。盐酸米诺环素（0-40 mg/kg，IP，一次）可显着抑制 METH 诱导的小鼠过度运动和行为敏化 [2]。在暂时性大脑中动脉闭塞 (TMCAO) 模型中，盐酸米诺环素（静脉注射 3 和 10 mg/kg 一次）可有效减少梗塞面积 [1]。盐酸米诺环素（3-10 mg/kg，静脉注射一次）对血液的影响可能会因电位诱发的室性心律失常而减轻。标准 200 mg 剂量对人体的这种作用可能与线粒体 KATP 通道、PI3K/Akt 信号传导和 L 型水平 (3 mg/kg) 有关[1]。

细胞增殖检测[3]
细胞类型：人卵巢癌细胞系（OVCAR-1α抑制，以及up-p53蛋白和AKT水平的调节/mTOR/p70S6K/4E-BP1失活染料 [6]。3. SKOV-3 和 A2780）和原代细胞（HEK-293、HMEC、HUVEC、ATCC）
测试浓度：0、1、10、50 和 100 μM
孵育时间：24、48或72小时
实验结果：抑制OVCAR-3、SKOV-3的增殖和A2780细胞呈浓度依赖性，IC50值分别为62.0、56.1和59.5 μM。对 HEK-293 或 HUVEC 的活力没有影响。

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蛋白质印迹分析[3]
细胞类型： OVCAR-3、SKOV-3 和 A2780 细胞
测试浓度： 0、 10、50 和 100 μM
孵育时间：72 小时
实验结果： Cyclins A、B 和 E 低表达水平。 caspase- 增加 3 个水平，在 100 μM 时增加超过 3.0 倍。米诺环素激活的 caspase-3 进而导致 PARP-1 的裂解。 Caspase-3 增加 PARP-1、p89 的降解产物。

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细胞周期分析[3]
细胞类型： OVCAR-3、SKOV-3 和 A2

Animal/Disease Models: Female nude mice (6 weeks old, 9 mice per group, each mouse was injected with OVCAR-3 cells subcutaneously (sc) (sc) on the left side of the abdomen) [3]
Doses: 10 or 30 mg/kg
Route of Administration: Orally in drinking water Administration, starting on day 8 of cell inoculation, one time/day for 4 weeks.
Experimental Results: Inhibited OVCAR-3 tumor growth and diminished microvessel density in these female nude mice.

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Animal/Disease Models: Male Balb/cAnNCrICrIj mice (8 weeks old, 23-30 g, methamphetamine (METH, 3 mg/kg) subcutaneously (sc) (sc) (sc) in a volume of 10 ml/kg) [2]
Doses: 0, 10 , 20 or 40 mg/kg
Route of Administration: intraperitoneal (ip) injection, once, 30 minutes before METH administration
Experimental Results: Significantly attenuated METH-induced hyperlocomotion and the development of behavioral sensitization in mice at 40 mg/kg. Did not exert any effect on the induction of METH-induced hyperthermia in mice. Significantly attenuated the reduction of DA and DOPAC in the striatum. Significantly attenuated the reduction of DAT-immunoreactivity in the mouse striatum. Significantly attenuated the increase in MAC1-immunoreactivity in the striatum after the administration of METH.

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Animal/Disease Models: Male Sprague-Dawley rats (270-330 g, TMCAO model)[1]
Doses: 3 mg/kg and 10 mg/kg
Route of Administration: IV, once, 4, 5, or 6 hours post TMCAO
Experimental Results: Reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56% at doses of 3 mg/kg; significantly reduced infarct size at 5 hours by 40% at doses of 10 mg/kg and the 3 mg/kg dose significantly reduced infarct size by 34%. With a 6 hour time window there was a non-significant trend in infarct reduction.

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Animal/Disease Models: Male Sprague-Dawley rats (270-330 g)[1]
Doses: 3, 10, or 20 mg/kg
Route of Administration: IV, once
Experimental Results: Peak concentrations of serum levels of minocycline averaged 3.6, 13.0 and 28.8 mg/L with 3, 10 and 20 mg/kg doses respectively. The serum levels of minocycline at a 3 mg/kg dose (3.6 mg/L) were similar to that reported in humans after a standard 200 mg dose. Did not significantly affect hemodynamic and physiological variables.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Many reviews state that tetracyclines are contraindicated during breastfeeding because of possible staining of infants' dental enamel or bone deposition of tetracyclines. However, a close examination of available literature indicates that there is not likely to be harm in short-term use of minocycline during lactation because milk levels are low and absorption by the infant is inhibited by the calcium in breastmilk. Short-term use of minocycline is acceptable in nursing mothers. As a theoretical precaution, avoid prolonged or repeat courses during nursing. Monitor the infant for rash and for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash). Black discoloration of breastmilk has been reported with minocycline. Topical minocycline for acne by the mother poses no risk to the breastfed infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
A woman taking minocycline 100 mg twice daily for almost 4 years developed galactorrhea after taking perphenazine, amitriptyline and diphenhydramine, and the breast secretion was black in color.
Another woman who had nursed her infant and produced occasional small amounts of breastmilk during the 18 months after weaning was given oral minocycline 150 mg daily. After 3 to 4 weeks, expressed milk had become black. Iron levels in milk were over 100 times greater than that found in normal milk. A mammogram was normal.
In both of these cases, macrophages containing a black, iron-containing pigment were found in milk. It is thought that the pigment is an iron chelate of minocycline or one of its metabolites.

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

[2]. 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]. Minocycline inhibits growth of epithelial ovarian cancer. Gynecol Oncol. 2012 May;125(2):433-40.

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

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

[6]. 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.

Minocycline Hydrochloride (internal use) can cause developmental toxicity according to state or federal government labeling requirements.
A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.
See also: Minocycline Hydrochloride (annotation moved to).

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Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections are extremely limited. Minocycline intravenous is active against many MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute breakpoints exist to guide interpretation of minocycline susceptibility results with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug Administration indication for treatment of infections caused by Acinetobacter. There is an accumulating amount of literature reporting successful use of minocycline intravenous for treatment of serious MDR Acinetobacter infections, particularly for nosocomial pneumonia. These results, coupled with the generally favorable tolerability of minocycline intravenous, support its use as a viable therapeutic option for treatment of MDR Acinetobacter infections. [5]

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Hypoxia-inducible factor (HIF)-1α is the key cellular survival protein under hypoxia, and is associated with tumor progression and angiogenesis. We have recently shown the inhibitory effects of minocycline on ovarian tumor growth correlated with attenuation of vascular endothelial growth factor (VEGF) and herein report a companion laboratory study to test if these effects were the result of HIF-1α inhibition. In vitro, human ovarian carcinoma cell lines (A2780, OVCAR-3 and SKOV-3) were utilized to examine the effect of minocycline on HIF-1 and its upstream pathway components to elucidate the underlying mechanism of action of minocycline. Mice harboring OVCAR-3 xenografts were treated with minocycline to assess the in vivo efficacy of minocycline in the context of HIF-1. Minocycline negatively regulated HIF-1α protein levels in a concentration-dependent manner and induced its degradation by a mechanism that is independent of prolyl-hydroxylation. The inhibition of HIF-1α was found to be associated with up-regulation of endogenous p53, a tumor suppressor with confirmed role in HIF-1α degradation. Further studies demonstrated that the effect of minocycline was not restricted to proteasomal degradation and that it also caused down-regulation of HIF-1α translation by suppressing the AKT/mTOR/p70S6K/4E-BP1 signaling pathway. Minocycline treatment of mice bearing established ovarian tumors, led to suppression of HIF-1α accompanied by up-regulation of p53 protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway. These data reveal the therapeutic potential of minocycline in ovarian cancer as an agent that targets the pro-oncogenic factor HIF-1α through multiple mechanisms.[6]

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Minocycline has been shown to protect against myocardial ischemia-reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45mg/kg, i.p.) 1h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K(ATP)) channels] which were once injected 10min before ischemia and then subjected to ischemia for 30min. Ventricular arrhythmias were assessed. L-type Ca(2+) current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P<0.05). The duration of VT+VF, the number of VT+VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P<0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT+VF, the number of VT+VF episodes and the severity of arrhythmias (P<0.05 for all). In addition, minocycline inhibited L-type Ca(2+) currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K(ATP) channels and L-type Ca(2+) channels may be involved.[7]

C23H28CLN3O7

493.9373

493.161

C, 55.93; H, 5.71; Cl, 7.18; N, 8.51; O, 22.67

13614-98-7

Minocycline;10118-90-8; Minocycline hydrochloride;13614-98-7;Minocycline-d6;1036070-10-6; 128420-71-3 (HCl hydrate)

54685925

Light yellow to yellow solid powder

659.4ºC at 760mmHg

205-210° (dec)

352.6ºC

6.33E-28mmHg at 25°C

1.688

164.63

6

9

3

34

971

4

CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=CC(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)O)O)N(C)C.Cl

KDLQIOPKJDNQIM-YKWOUSISSA-N

InChI=1S/C23H27N3O7.ClH/c1-25(2)12-5-6-13(27)15-10(12)7-9-8-11-17(26(3)4)19(29)16(22(24)32)21(31)23(11,33)20(30)14(9)18(15)28;/h5-6,9,11,17,27-28,32-33H,7-8,24H2,1-4H3;1H/b22-16+;/t9-,11-,17+,23-;/m1./s1

(4S,4aR,5aS,12aR,E)-2-(amino(hydroxy)methylene)-4,7-bis(dimethylamino)-10,11,12a-trihydroxy-4a,5a,6,12a-tetrahydrotetracene-1,3,12(2H,4H,5H)-trione hydrochloride

NSC 141993; Minocycline HCl; NSC 141993; Mynocine hydrochloride; NSC141993; NSC-141993; Periocline; Klinomycin; Minocin; Solodyn; Mynocine; Tri-mino; Vectrin; Ximino; Minomax; Minomycin chloride; Mynocine hydrochloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~19.23 mg/mL (~38.93 mM)
H2O : ~9.09 mg/mL (~18.40 mM)

配方 1 中的溶解度: 7.69 mg/mL (15.57 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。