Minocycline hydrochloride 是一种口服有效、能透过血脑屏障的半合成四环素类抗生素。Minocycline hydrochloride 是一种缺氧诱导因子 (HIF-1α) 抑制剂。Minocycline hydrochloride 具有抗癌(anti-cancer)，抗炎(anti-inflammatory) 和谷氨酸 (glutamate) 拮抗作用。Minocycline hydrochloride 降低谷氨酸神经传递，显示神经保护特性和抗抑郁作用。Minocycline hydrochloride 通过与细菌核糖体30S亚基结合，抑制细菌蛋白的合成，从而产生抑菌 (bacteriostatic) 作用。
| 生物活性 | Minocycline hydrochloride is an orally active, potent and BBB-penetrated semi-synthetictetracyclineantibiotic. Minocycline hydrochloride is ahypoxia-inducible factor (HIF)-1αinhibitor. Minocycline hydrochloride showsanti-cancer,anti-inflammatory, andglutamateantagonist effects. Minocycline hydrochloride reduces glutamate neurotransmission and shows neuroprotective properties and antidepressant effects. Minocycline hydrochloride inhibitsbacterialprotein synthesis through binding with the 30S subunit of thebacterialribosome, resulting in abacteriostaticeffect[1][2][3][4][5][6][7]. |
| IC50& Target | Tetracycline | L-type calcium channel |
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体外研究
(In Vitro) | Minocycline hydrochloride (0-100 μM, 24-72 h) suppresses proliferation and clonogenic activity of ovarian cancer cell-lines (OVCAR-3, SKOV-3 and A2780)[3].
Minocycline hydrochloride (0-100 μM, 24-48 h)arrests cell cycle through inhibition of cyclins and suppression of DNA incorporation[3].
Minocycline hydrochloride (0-100 μM, 72 h) induces cell apoptosis in ovarian cancer cell lines[3].
Minocycline hydrochloride shows direct neuronal protection, and this mode of protection is likely to be associated with the preservation of mitochondrial integrity and cytochrome c, followed by the suppression of caspase-dependent as well as caspase-independent cell death[2].
Minocycline hydrochloride leads to suppression of Hypoxia-inducible factor (HIF)-1α accompanied by up-regulation of p53 protein levels and inactivation of AKT/mTOR/p70S6K/4E-BP1 pathway[6].
Cell Proliferation Assay[3] | Cell Line: | Human ovarian cancer cell lines (OVCAR-3, SKOV-3 and A2780) and primary cells (HEK-293, HMEC, HUVEC, ATCC) | | Concentration: | 0, 1, 10, 50 and 100 μM | | Incubation Time: | 24, 48 or 72 h | | Result: | Inhibited proliferation of OVCAR-3, SKOV-3 and A2780 cells in a concentration-dependent manner, with IC50values of 62.0, 56.1 and 59.5 μM, respectively. Had no effect on the viability of HEK-293 or HUVEC. |
Western Blot Analysis[3] | Cell Line: | OVCAR-3, SKOV-3 and A2780 cells | | Concentration: | 0, 10, 50 and 100 μM | | Incubation Time: | 72 h | | Result: | Expressed lower levels of cyclins A, B and E. Increased caspase-3 levels by more than 3.0 fold in the 100 μM. Minocycline-activated caspase-3 in turn led to cleavage of PARP-1. Increased the degradation product p89 of PARP-1 by caspase-3. |
Cell Cycle Analysis[3] | Cell Line: | OVCAR-3, SKOV-3 and A2780 cells | | Concentration: | 0, 10, 50 and 100 μM | | Incubation Time: | 24 or 48 h | | Result: | Arrested cells in the G0-G1 phase in a concentration and time-dependent manner. Declined percentage of cells in the S and G2-M phases in excess of 80% each at 100 μM. |
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体内研究
(In Vivo) | Minocycline hydrochloride (0-30 mg/kg, orally, daily for 4 weeks) suppresses OVCAR-3 tumor growth in female nude mice[3].
Minocycline hydrochloride (IP) is an effective neuroprotective agent in animal models of cerebral ischemia when given in high doses intraperitoneally[1].
Minocycline hydrochloride (0-40 mg/kg, IP, once) significantly attenuats METH-induced hyperlocomotion and the development of behavioral sensitization in mice[2].
Minocycline hydrochloride (3 and 10 mg/kg, IV, once) is effective at reducing infarct size in a Temporary Middle Cerebral Artery Occlusion model (TMCAO)[1].
Minocycline hydrochloride (3-10 mg/kg, IV, once) results in serum levels (at 3 mg/kg) similar to that achieved in humans after a standard 200 mg dose[1].
Minocycline hydrochloride attenuates ischemia-induced ventricular arrhythmias in rats. This effect may be associated with activations of PI3K/Akt signaling pathway, mitochondrial KATP channels and L-type Ca2+ channels[7].
| Animal Model: | Female nude mice (6 weeks old, 9 per group, OVCAR-3 cells were injected s.c. into the left flank of each mouse)[3] | | Dosage: | 10 or 30 mg/kg | | Administration: | Administered orally in the drinking water, initiated on day 8 of cell inoculation, daily for 4 weeks | | Result: | Suppressed OVCAR-3 tumor growth in these female nude mice, and reduced microvessel density. |
| Animal Model: | Male Balb/cAnNCrICrIj mice (8 weeks old, 23-30 g, methamphetamine (METH, 3 mg/kg) was injected subcutaneously (s.c.) in a volume of 10 ml/kg)[2] | | Dosage: | 0, 10, 20, or 40 mg/kg | | Administration: | IP, once, 30 min before the administration of METH | | Result: | 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. |
| Animal Model: | Male Sprague-Dawley rats (270-330 g, TMCAO model)[1] | | Dosage: | 3 mg/kg and 10 mg/kg | | Administration: | IV, once, 4, 5, or 6 hours post TMCAO | | Result: | 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. |
| Animal Model: | Male Sprague-Dawley rats (270-330 g)[1] | | Dosage: | 3, 10, or 20 mg/kg | | Administration: | IV, once | | Result: | 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. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : 19.23 mg/mL(38.93 mM;Need ultrasonic) H2O : 10 mg/mL(20.25 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.0245 mL | 10.1227 mL | 20.2454 mL | | 5 mM | 0.4049 mL | 2.0245 mL | 4.0491 mL | | 10 mM | 0.2025 mL | 1.0123 mL | 2.0245 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
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