Mevastatin   中文名称: 美伐他汀

用左氧氟沙星（0–128 μM；5 天；Caco-2 细胞）治疗以剂量依赖性方式减少细胞数量 [1]。用美伐他汀（32-128 μM；24-72 小时；Caco-2 细胞）治疗会导致细胞周期停滞在两个阶段：早期 G0/G1 和晚期 G2/M [1]。 Caco-2 细胞经美伐他汀 (32-128 μM) 处理 72 小时后，细胞周期蛋白依赖性激酶 (cdk) 4 和 6 以及细胞周期蛋白 D1 下调；相反，cdk 2 和 cdk E 蛋白的水平保持不变。美伐他汀显着增加 p21 和 p27 这两种细胞周期抑制剂 [1]。美伐他汀（16-256 μM；Caco-2 细胞）治疗剂量依赖性地促进细胞凋亡 [1]。美伐他汀处理 Neuro2a 细胞 24 小时导致神经突生长并增加神经元标记蛋白 NeuN 的表达。重要的激酶 ERK1/2、Akt/蛋白激酶 B 和表皮生长因子受体 (EGFR) 在美伐他汀的作用下发生磷酸化。美伐他汀诱导的轴突发育受到 PI3K、EGFR 和丝裂原激活蛋白激酶级联抑制的抑制 [4]。

在野生型 129-SV/eVTAcBr 雄性小鼠和 eNOS 缺陷雄性小鼠中，美伐他汀（2-20 mg/kg；每天通过 ALZET 微渗透泵给药）可增加内皮一氧化氮合成酶 (eNOS) mRNA 和蛋白质的水平，降低梗死面积，并以剂量和时间依赖性方式改善神经功能缺损[2]。局部施用美伐他汀（2.5 pmol/小时）除了促进骨转换外，还可促进骨形态发生蛋白 2 (BMP-2) mRNA 和 NF-κB 配体受体激活剂 (RANKL) mRNA 表达。 MRL/MpJ 小鼠的移植骨量[3]。

细胞活力测定[2]
细胞类型： Caco-2 细胞
测试浓度： 0 µM、8 µM、16 µM、32 µM、64 µM ，128 µM
孵育时间： 5 天
实验结果： 导致细胞数量呈剂量依赖性减少。

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细胞周期分析[2]
细胞类型： Caco-2 细胞
测试浓度： 32 µM、64 µM、128 µM
孵化持续时间：24小时、48小时、72小时
实验结果：引起剂量依赖性增加细胞处于细胞周期的 G0/G1 和 G2/M 期。

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蛋白质印迹分析[2]
细胞类型： Caco-2 细胞
测试浓度： 32 µM、64 µM、128 µM
孵育持续时间：72 小时
实验结果：导致细胞周期蛋白依赖性激酶 (cdk ) 4 和 cdk 6 下调以及细胞周期蛋白 D1。

Animal/Disease Models: Wild-type 129-SV/eVTAcBr male mice and eNOS-deficient male mice (18-22 g) with the filament model[2]
Doses: 2 mg/kg or 20 mg/kg
Route of Administration: Delivered via 7- or 14-day ALZET miniosmotic pumps implanted subcutaneously (sc); daily; for 7, 14, or 28 days
Experimental Results: Increased levels of endothelial nitric oxide synthase (eNOS) mRNA and protein, decreased infarct size, and improved neurological deficits in a dose- and time- dependent manner.

[1]. Wächtershäuser A, et al. HMG-CoA reductase inhibitor mevastatin enhances the growth inhibitory effect of butyrate in the colorectal carcinoma cell line Caco-2. Carcinogenesis. 2001 Jul;22(7):1061-7.
[2]. Amin-Hanjani S, Stagliano NE, Yamada M, et al. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke. 2001 Apr;32(4):980-6.
[3]. Sugazaki M, Hirotani H, Echigo S, et al. Effects of mevastatin on grafted bone in MRL/MpJ mice. Connect Tissue Res. 2010 Apr;51(2):105-12.
[4]. Evangelopoulos ME, Weis J, Krüttgen A. Mevastatin-induced neurite outgrowth of neuroblastoma cells via activation of EGFR. J Neurosci Res. 2009 Jul;87(9):2138-44.

Mevastatin is a carboxylic ester that is pravastatin that is lacking the allylic hydroxy group. A hydroxymethylglutaryl-CoA reductase inhibitor (statin) isolated from Penicillium citrinum and from Penicillium brevicompactum, its clinical use as a lipid-regulating drug ceased following reports of toxicity in animals. It has a role as a fungal metabolite, an EC 3.4.24.83 (anthrax lethal factor endopeptidase) inhibitor, an antifungal agent, a Penicillium metabolite and an apoptosis inducer. It is a carboxylic ester, a statin (naturally occurring), a member of hexahydronaphthalenes, a member of 2-pyranones and a polyketide.
Mevastatin or compactin is a cholesterol-lowering agent isolated from Penicillium citinium. It was the first discovered agent belonging to the class of cholesterol-lowering medications known as statins. During a search for antibiotic compounds produced by fungi in 1971, Akira Endo at Sankyo Co. (Japan) discovered a class of compounds that appeared to lower plasma cholesterol levels. Two years later, the research group isolated a compound structurally similar to hydroxymethylglutarate (HMG) that inhibited the incorporation of acetate. The compound was proposed to bind to the reductase enzyme and was named compactin. Mevastatin is a competitive inhibitor of HMG-Coenzyme A (HMG-CoA) reductase with a binding affinity 10,000 times greater than the HMG-CoA substrate itself. Mevastatin is a pro-drug that is activated by in vivo hydrolysis of the lactone ring. It has served as one of the lead compounds for the development of the synthetic compounds used today.
Mevastatin has been reported in Penicillium cyclopium, Morus lhou, and other organisms with data available.
Mevastatin is an HMG-CoA reductase inhibitor that was initially isolated from the mold Pythium ultimum. Mevastatin was the first statin to enter clinical trials.

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Not used therapeutically due to its many side effects.

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Mevastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Mevastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with 10,000 times greater affinity than its natural substrate. The bicyclic portion of mevastatin binds to the coenzyme A portion of the active site.

C23H34O5

390.51

390.24

73573-88-3

64715

Typically exists as solid at room temperature

1.1±0.1 g/cm3

555.0±50.0 °C at 760 mmHg

151-153 °C

186.5±23.6 °C

0.0±3.4 mmHg at 25°C

1.535

3.57

72.83

1

5

7

28

637

7

O(C([C@@]([H])(C([H])([H])[H])C([H])([H])C([H])([H])[H])=O)[C@@]1([H])C([H])([H])C([H])([H])C([H])=C2C([H])=C([H])[C@]([H])(C([H])([H])[H])[C@]([H])(C([H])([H])C([H])([H])[C@]3([H])C([H])([H])[C@]([H])(C([H])([H])C(=O)O3)O[H])[C@@]12[H]

AJLFOPYRIVGYMJ-INTXDZFKSA-N

InChI=1S/C23H34O5/c1-4-14(2)23(26)28-20-7-5-6-16-9-8-15(3)19(22(16)20)11-10-18-12-17(24)13-21(25)27-18/h6,8-9,14-15,17-20,22,24H,4-5,7,10-13H2,1-3H3/t14-,15-,17+,18+,19-,20-,22-/m0/s1

[(1S,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

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

配方 1 中的溶解度: ≥ 2.5 mg/mL (6.40 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (6.40 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (6.40 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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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。