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

OVCAR-3、SKOV-3 和 A2780 是卵巢癌细胞系，其增殖和克隆活性受到米诺环素（0-100 μM，24-72 小时）的抑制 [3]。米诺环素（0-100 μM，24-48 小时）抑制 DNA 掺入和细胞周期蛋白，从而停止细胞周期 [3]。当暴露于米诺环素 (0-100 μM) 72 小时时，卵巢癌细胞系会发生凋亡 [3]。米诺环素在表现出直接神经元保护作用后，可抑制 caspase 依赖性和 caspase 非依赖性细胞死亡，这种保护机制可能与线粒体完整性和细胞色素 c 的维持有关 [2]。缺氧诱导因子 (HIF)-1α 受到米诺环素的抑制，米诺环素还会增加 p53 蛋白水平并停用 AKT/mTOR/p70S6K/4E-BP1 通路 [6]。

在雌性裸鼠中，每天口服一次米诺环素（0-30 mg/kg），持续四个星期，可抑制 OVCAR-3 肿瘤的生长[3]。当腹腔内给予大剂量时，米诺环素（IP）是脑缺血动物模型中的一种神经保护剂[1]。小鼠单次腹腔注射米诺环素（0-40 mg/kg）可以大大减少METH引起的行为过敏和过度运动的发生[2]。暂时性大脑中动脉闭塞模型（TMCAO）一次性静脉注射3或10 mg/kg米诺环素可有效缩小梗死面积[1]。米诺环素（3-10 mg/kg IV，一次）的血清水平（3 mg/kg）与人类典型 200 mg 剂量后所达到的水平相当[1]。米诺环素可减轻大鼠缺血引起的室性心律失常。 L 型 Ca2+ 通道、线粒体 KATP 通道和 PI3K/Akt 信号通路的激活可能与这种效应有关 [7]。

细胞增殖测定[3]
细胞类型： 人卵巢癌细胞系（OVCAR-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： 以浓度依赖性方式抑制OVCAR-3、SKOV-3和A2780细胞的增殖，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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细胞周期分析[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：24 或 48 小时
实验结果：G0-G1 期细胞被封闭依赖于时间的方式。在 100 μM 时，S 期和 G2-M 期细胞的百分比减少了 80% 以上。

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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。米诺西

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: Oral administration through drinking water The drug was administered one time/day starting on the 8th day of cell inoculation for 4 weeks.
Experimental Results: Inhibited the growth of OVCAR-3 tumors in these female nude mice and diminished microvessel density.

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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: At the 40 mg/kg dose, the development of METH-induced hyperlocomotion and behavioral hypersensitivity was Dramatically attenuated in mice. It had no effect on the induction of METH-induced hyperthermia in mice. Dramatically attenuated reductions in DA and DOPAC in the striatum. S

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 is a tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5. It has a role as an antibacterial drug, an Escherichia coli metabolite and a geroprotector. It is a member of tetracyclines, a tetracenomycin and a tertiary alpha-hydroxy ketone. It is a conjugate acid of a minocycline(1-). It is a tautomer of a minocycline zwitterion.
Minocycline is a Tetracycline-class Drug. The physiologic effect of minocycline is by means of Decreased Prothrombin Activity.
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 (annotation moved to).

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Background: Minocycline, a semi-synthetic tetracycline antibiotic, is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally. The aim of this study was to determine if minocycline was effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO) when given at lower intravenous (IV) doses that correspond to human clinical exposure regimens. Methods: Rats underwent 90 minutes of TMCAO. Minocycline or saline placebo was administered IV starting at 4, 5, or 6 hours post TMCAO. Infarct volume and neurofunctional tests were carried out at 24 hr after TMCAO using 2,3,5-triphenyltetrazolium chloride (TTC) brain staining and Neurological Score evaluation. Pharmacokinetic studies and hemodynamic monitoring were performed on minocycline-treated rats. Results: Minocycline at doses of 3 mg/kg and 10 mg/kg IV was effective at reducing infarct size when administered at 4 hours post TMCAO. At doses of 3 mg/kg, minocycline reduced infarct size by 42% while 10 mg/kg reduced infarct size by 56%. Minocycline at a dose of 10 mg/kg significantly reduced infarct size at 5 hours by 40% 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. There was a significant difference in neurological scores favoring minocycline in both the 3 mg/kg and 10 mg/kg doses at 4 hours and at the 10 mg/kg dose at 5 hours. Minocycline did not significantly affect hemodynamic and physiological variables. A 3 mg/kg IV dose of minocycline resulted in serum levels similar to that achieved in humans after a standard 200 mg dose. Conclusions: The neuroprotective action of minocycline at clinically suitable dosing regimens and at a therapeutic time window of at least 4-5 hours merits consideration of phase I trials in humans in view of developing this drug for treatment of stroke. [1]

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The effects of minocycline on behavioral changes and neurotoxicity in the dopaminergic neurons induced by the administration of methamphetamine (METH) were studied. Pretreatment with minocycline (40 mg/kg) was found to attenuate hyperlocomotion in mice after a single administration of METH (3 mg/kg). The development of behavioral sensitization after repeated administration of METH (3 mg/kg/day, once daily for 5 days) was significantly attenuated by pretreatment with minocycline (40 mg/kg). A reduction in the level of dopamine (DA) and its major metabolite, 3,4-dihydroxyphenyl acetic acid (DOPAC), in the striatum after the repeated administration of METH (3 mg/kg x 3, 3-h interval) was attenuated in a dose-dependent manner by pretreatment with and the subsequent administration of minocycline (10, 20, or 40 mg/kg). Furthermore, minocycline (40 mg/kg) significantly attenuated a reduction in DA transporter (DAT)-immunoreactivity in the striatum after repeated administration of METH. In vivo microdialysis study demonstrated that pretreatment with minocycline (40 mg/kg) significantly attenuated increased extracellular DA levels in the striatum after the administration of METH (3 mg/kg). In addition, minocycline was not found to alter the concentrations of METH in the plasma or the brain after three injections of METH (3 mg/kg), suggesting that minocycline does not alter the pharmacokinetics of METH in mice. Interestingly, METH-induced neurotoxicity in the striatum was significantly attenuated by the post-treatment and subsequent administration of minocycline (40 mg/kg). These findings suggest that minocycline may be able to ameliorate behavioral changes as well as neurotoxicity in dopaminergic terminals after the administration of METH. Therefore, minocycline could be considered as a useful drug for the treatment of several symptoms associated with METH abuse in humans.[2]

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Objective: These studies were designed to determine whether minocycline inhibits ovarian cancer growth in vitro and in vivo and the molecular mechanisms involved. Materials and methods: The effect of minocycline on ovarian cancer cell proliferation, cell cycle progression and apoptosis was assessed using human ovarian cancer cell lines OVCAR-3, SKOV-3 and A2780. Then, the capacity of minocycline to inhibit growth of OVCAR-3 xenografts in female nude mice was examined. Results: Minocycline inhibited cell proliferation and colony formation, down-regulated cyclins A, B and E leading to arrest of cells in the G(0) phase of the cycle and suppression of DNA synthesis. Furthermore, exposure of these cells to minocycline led to DNA laddering, activation of caspase-3 and cleavage of PARP-1. In nude mice bearing sub-cutaneous tumors, minocycline suppressed tumor proliferation index, angiogenesis and tumor growth. Conclusion: These findings provide the initial basis for further evaluation of minocycline in the treatment of ovarian cancer.[3]

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This study tested the potential antidepressant activity of minocycline alone or combined with two traditional antidepressant drugs or several glutamate receptor antagonists, using the time sampling method in the forced swimming test. Results showed that: desipramine (10.0 mg/kg, P<0.05; 15.0 mg/kg, P<0.05), minocycline (60.0 mg/kg, P<0.05; 80.0 mg/kg, P<0.05) and EMQMCM (1.5 mg/kg, P<0.05; 2.0 mg/kg, P<0.05), reduced immobility by increasing climbing. Fluoxetine (20.0 mg/kg, P<0.05; 25.0 mg/kg, P<0.05) reduced immobility by increasing swimming. MTEP (5.0 mg/kg, P<0.05; 10.0 mg/kg, P<0.05) and dizolcipine (1.0 mg/kg, P<0.05; 1.5 mg/kg, P<0.05) reduced immobility by increasing swimming and climbing. Combination experiments showed that a subthreshold dose of minocycline (50.0 mg/kg) synergized the antidepressant-like actions of subthreshold doses of: desipramine (5.0 mg/kg; P<0.05), EMQMCM (0.6 mg/kg; P<0.05), MTEP (2.5 mg/kg; P<0.05) and dizolcipine (0.5 mg/kg; P<0.05). In conclusion, minocycline produced antidepressant-like actions in the FST and subthreshold dose of minocycline combined with subthreshold dose of desipramine and several glutamate receptor antagonists and produced antidepressant-like actions.[4]

C23H27N3O7

457.48

457.184

C, 60.39; H, 5.95; N, 9.19; O, 24.48

10118-90-8

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

54675783

Typically exists as green solid at room temperature

1.6±0.1 g/cm3

803.3±65.0 °C at 760 mmHg

439.6±34.3 °C

0.0±3.0 mmHg at 25°C

1.718

-0.65

164.63

5

9

3

33

971

4

CN(C1=CC=C(O)C2=C1C[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C([C@@]4(O)C(O)=C3C2=O)=O)C

FFTVPQUHLQBXQZ-KVUCHLLUSA-N

InChI=1S/C23H27N3O7/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/h5-6,9,11,17,27-28,31,33H,7-8H2,1-4H3,(H2,24,32)/t9-,11-,17-,23-/m0/s1

(4S,4aS,5aR,12aR)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide

HSDB3130; HSDB-3130; HSDB 3130

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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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;
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