辛伐他汀是一种无活性的药物前体，需要在肝脏中分解成羟基酸形式才能开始发挥作用。它本身没有药物活性。在体外测试中，氢氧化钠（NaOH）可以激活它。 Simvastatin 的 IC50 值分别为 19.3 nM、13.3 nM 和 15.6 nM，抑制小鼠 LM 细胞、大鼠 H4II E 细胞和人 Hep G2 细胞中胆固醇的合成[1]。 30分钟内，辛伐他汀以剂量依赖性方式增加Akt的丝氨酸473磷酸化；峰值磷酸化发生在 1.0 µM[2]。辛伐他汀 (1.0 μM) 抑制无血清培养基发生细胞凋亡，加速血管结构的形成，并增加内源性 Akt 底物内皮一氧化氮合酶 (eNOS) 的磷酸化[2]。辛伐他汀具有抗炎特性，可减少 10 μM 的 IFN-γ 释放，以及抗 CD3/抗 CD28 抗体诱导的 PB 衍生单核细胞和类风湿性关节炎血液滑膜氟细胞的增殖 [3]。此外，大约 30% 通过同源接触产生的细胞介导的巨噬细胞 TNF-γ 释放被辛伐他汀 (10 μM) 阻断[3]。在星形胶质细胞和神经母细胞瘤细胞中，辛伐他汀 (5 μM) 显着降低星形胶质细胞中 ABCA1 表达、载脂蛋白 E 表达，并增强 SK-N-SH 细胞中糖原合成酶激酶 3β 和细胞周期蛋白依赖性激酶 5 表达 [7]。辛伐他汀可以抑制外泌体的释放[10]。辛伐他汀在 32 和 64 μM 时可减缓肿瘤细胞发育并使其停止在 G0/G1 期； 24、48 和 72 小时[11]。在 HepG2 和 Huh7 细胞中，辛伐他汀（32 和 64 μM；48 小时）会导致细胞凋亡[11]。

口服给药时，辛伐他汀可抑制放射性标记的乙酸盐转化为胆固醇，IC50 为 0.2 mg/kg[1]。在喂食富含致动脉粥样硬化胆固醇饮食的兔子中，辛伐他汀（4 毫克/天，口服 13 周）可将总胆固醇、低密度脂蛋白胆固醇和高密度脂蛋白胆固醇的增加逆转至正常水平[4]。在饲喂含有 0.25% 胆固醇的饮食的兔子中，辛伐他汀 (6 mg/kg) 会增加肝脏 LDL 受体的数量和 LDL 受体依赖性结合[5]。在饲喂致动脉粥样硬化饮食的食蟹猴中，辛伐他汀（20 mg/kg/天）导致病变处巨噬细胞含量减少 1.3 倍，血管细胞粘附分子-1、白细胞介素-1β 和组织因子表达减少 2 倍。这些减少伴随着病变平滑肌细胞和胶原蛋白含量增加 2.1 倍[6]。辛伐他汀治疗（口服灌胃；每日一次；14天）； 15 和 30 mg/kg）可减少氧化损伤、TNF-a 和 IL-6 水平，并恢复线粒体酶复合物的活性[12]。

细胞增殖测定[11]
细胞类型： HepG2 和 Huh7 细胞
测试浓度： 32 和 64 μM
孵育时间： 24、48 和 72 小时
实验结果：与对照相比，抑制肿瘤细胞生长（ctrl，p<0.05）。

---

细胞凋亡分析[11]
细胞类型： HepG2 和 Huh7 细胞
测试浓度： 32 和 64 μM
孵育持续时间：48 小时
实验结果：早期凋亡率从未处理的 ctrl 细胞中的 9.2% 增加到 18.2% (32 μM) 和 19.8% (64 μM) 分别将晚期细胞凋亡从 ctrl 细胞中的 35.0% 增加到 HepG2 细胞中的 56.9% (32 μM) 和 48.0% (64 μM)。

---

细胞周期分析[11]
细胞类型： HepG2 和 Huh7 细胞
测试浓度： 32 和 64 μM
<孵化持续时间：24、48 和 72 小时
实验结果：与 ctrl 肿瘤相比，CDK1、CDK2、CDK4 以及细胞周期蛋白 D1 和 E 下调细胞。

Animal/Disease Models: Male wistar rats with oxidative damage by Intrastriatal 6-OHDA administration[12]
Doses: 15 and 30 mg/kg
Route of Administration: po (oral gavage); 15 and 30 mg/kg; one time/day; 14 days
Experimental Results: Attenuated oxidative damage (decreased MDA, nitrite levels and restoration of decreased GSH), attenuated TNF-a and IL-6 levels, and restored itochondrial enzyme complex activities as compared to 6-OHDA group.

[1]. Slater, E.E., et al. Mechanism of action and biological profile of HMG CoA reductase inhibitors. A new therapeutic alternative. Drugs, 1988. 36 Suppl 3: p. 72-82.
[2]. Kureishi, Y., et al. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat Med, 2000. 6(9): p. 1004-10.
[3]. Leung BP, et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J Immunol. 2003 Feb 1;170(3):1524-30.
[4]. Kobayashi M, et al. Preventive effect of MK-733 (simvastatin), an inhibitor of HMG-CoA reductase, on hypercholesterolemia and atherosclerosis induced by cholesterol feeding in rabbits. Jpn J Pharmacol. 1989 Jan;49(1):125-33.
[5]. Ishida F, et al. Comparative effects of simvastatin (MK-733) and CS-514 on hypercholesterolemia induced by cholesterol feeding in rabbits. Biochim Biophys Acta. 1990 Feb 23;1042(3):365-73.
[6]. Sukhova GK, et al. Statins reduce inflammation in atheroma of nonhuman primates independent of effects on serum cholesterol. Arterioscler Thromb Vasc Biol. 2002 Sep 1;22(9):1452-8.
[7]. Weijiang Dong, et al. Differential effects of simvastatin and CS-514 on expression of Alzheimer’s disease-related genes in human astrocytes and neuronal cells. J Lipid Res. 2009 Oct; 50(10): 2095-2102.
[8]. Liu Z, et al. Pretreatment Donors after Circulatory Death with Simvastatin Alleviates Liver Ischemia Reperfusion Injury through a KLF2-Dependent Mechanism in Rat. Oxid Med Cell Longev. 2017;2017:3861914.
[9]. Ifergan I, et al. Statins reduce human blood-brain barrier permeability and restrict leukocyte migration: relevance to multiple sclerosis. Ann Neurol. 2006 Jul;60(1):45-55.
[10]. Zhang H, et al. Advances in the discovery of exosome inhibitors in cancer. J Enzyme Inhib Med Chem. 2020;35(1):1322-1330.
[11]. Borna Relja, et al. Simvastatin inhibits cell growth and induces apoptosis and G0/G1 cell cycle arrest in hepatic cancer cells. Int J Mol Med. 2010 Nov;26(5):735-41.
[12]. Anil Kumar, et al. Neuroprotective potential of atorvastatin and simvastatin (HMG-CoA reductase inhibitors) against 6-hydroxydopamine (6-OHDA) induced Parkinson-like symptoms. Brain Res. 2012 Aug 30;1471:13-22.

C25H38O5

418.57

79902-63-9

Simvastatin-d6;1002347-71-8;Simvastatin-d11;1002347-74-1;Simvastatin-d3;1002347-61-6

C[C@H]1C=CC2=C[C@H](C)C[C@H](OC(C(C)(C)CC)=O)C2[C@H]1CC[C@@H]3C[C@@H](O)CC(O3)=O

(1S,3R,7S,8S)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2,2-dimethylbutanoate

MK-0733, MK 0733, MK0733, Zocor; Synvinolin; MK 733; Sinvacor; MK-733; MK733; Simvastatin;

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: 2.5 mg/mL (5.97 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

Solubility in Formulation 5: ≥ 2.5 mg/mL (5.97 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 6: 2% DMSO+30% PEG 300+5% Tween80+ddH2O:10 mg/mL

---

Solubility in Formulation 7: 10 mg/mL (23.89 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

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。