Mevalonate (lithium salt)
(Synonyms: Mevalonic Acid, MVA, Pentanoic Acid) 目录号 : GC52250
Mevalonate (lithium salt)是甲羟戊酸途径的代谢前体。
Cas No.:2618458-93-6
Sample solution is provided at 25 µL, 10mM.
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Mevalonate (lithium salt) is a metabolic precursor of the mevalonate pathway[1]. As a substrate supplement for this pathway, Mevalonate (lithium salt) is mainly utilized to investigate its key role in cell growth, proliferation, cholesterol synthesis, and protein prenylation[2]. Mevalonate (lithium salt) is commonly used in research on cardiovascular diseases, neurological disorders, metabolic diseases, and cancer[3][4].
In vitro, treatment of FRTL-5 thyroid epithelial cells with Mevalonate (lithium salt) (700µM; 2h) completely reversed mevinolin-induced cytoskeletal disruption, restored polygonal morphology, reorganized actin stress fibers and cortical actin networks, and re-established microtubule architecture[5]. Mevalonate (lithium salt) (5-20mM; 8-72h) dose-dependently inhibited acid sphingomyelinase activity, increased cellular cholesterol levels, elevated sphingomyelin and phosphatidylcholine content, and suppressed proliferation in HepG2 and Caco-2 cells[6].
In vivo, Mevalonate (lithium salt) (100mg/kg/day; i.p.; 14 days) enhanced anti-PD-L1 antibody efficacy, upregulated tumor PD-L1 expression, increased CD8+ and CD3+ T cell infiltration, and elevated IFN-γ, IL-2, and TNF-α secretion in CT26 colon cancer-bearing BALB/c mice[7].
References:
[1] Dellas N, Thomas ST, Manning G, Noel JP. Discovery of a metabolic alternative to the classical mevalonate pathway. Elife. 2013;2:e00672.
[2] Goldstein JL, Brown MS. Regulation of the mevalonate pathway. Nature. 1990;343(6257):425-430.
[3] Buhaescu I, Izzedine H. Mevalonate pathway: a review of clinical and therapeutical implications. Clin Biochem. 2007;40(9-10):575-584.
[4] Juarez D, Fruman DA. Targeting the Mevalonate Pathway in Cancer. Trends Cancer. 2021;7(6):525-540.
[5] Bifulco M, Laezza C, Aloj SM, Garbi C. Mevalonate controls cytoskeleton organization and cell morphology in thyroid epithelial cells. J Cell Physiol. 1993;155(2):340-348.
[6] Chen Y, Xu SC, Duan RD. Mevalonate inhibits acid sphingomyelinase activity, increases sphingomyelin levels and inhibits cell proliferation of HepG2 and Caco-2 cells. Lipids Health Dis. 2015;14:130.
[7] Zhang W, Pan X, Xu Y, et al. Mevalonate improves anti-PD-1/PD-L1 efficacy by stabilizing CD274 mRNA. Acta Pharm Sin B. 2023;13(6):2585-2600.
Mevalonate (lithium salt)是甲羟戊酸途径的代谢前体[1]。Mevalonate (lithium salt)作为甲羟戊酸途径的底物补充剂，主要用于研究该途径在细胞生长、增殖、胆固醇合成及蛋白质异戊二烯化中的关键作用[2]。Mevalonate (lithium salt)通常用于心血管疾病、神经疾病、代谢疾病及癌症研究[3][4]。
在体外实验中，Mevalonate (lithium salt)（700µM；2小时）完全逆转了mevinolin诱导的FRTL-5甲状腺上皮细胞骨架破坏，恢复了多边形形态，重组了肌动蛋白应力纤维和皮质肌动蛋白网络，并重建了微管结构[5]。Mevalonate (lithium salt)（5-20mM；8-72小时）呈剂量依赖性抑制HepG2和Caco-2细胞中的酸性鞘磷脂酶活性，上调细胞内胆固醇水平，增加鞘磷脂和磷脂酰胆碱含量，并抑制细胞增殖[6]。
在体内实验中，Mevalonate (lithium salt)（100mg/kg/天；腹腔注射；14天）增强了抗PD-L1抗体的疗效，上调了肿瘤PD-L1表达，增加了CD8⁺和CD3⁺ T细胞浸润，并提升了CT26结肠癌荷瘤BALB/c小鼠肿瘤组织中IFN-γ、IL-2和TNF-α的分泌水平[7]。
| Cell experiment [1]: | |
Cell lines | HepG2 and Caco-2 cells |
Preparation Method | HepG2 and Caco-2 cells were cultured in monolayer in RPMI-1640 medium and DMEM medium, respectively, containing 4.5μg/l glucose, 2mM glutamine, 10% heat inactivated FBS, 100IU/ml penicillin and 10μg/ml streptomycin. Mevalonate (lithium salt) was dissolved in the culture medium as a stock and added in the cell culture medium to final concentrations examined. In the control group, only the culture medium was added. After incubation, the cells were scraped, lysed and sonicated. After centrifugation at 10000g at 4°C for 10min, the activities of SMases in the homogenate were determined. For kinetic studies, one day after the subculture, the cells were treated with Mevalonate (lithium salt) (5-20mM) for 8, 24, 48 and 72h and the acid SMase activities were determined. The changes of the activity after mevalonate treatment were expressed as percentage of the values before Mevalonate (lithium salt) treatment (0 time value). The cell proliferation was assay by MTT Cell Proliferation Assay kit. |
Reaction Conditions | 5-20mM; 8-72h |
Applications | Mevalonate (lithium salt) dose-dependently inhibited acid sphingomyelinase activity and suppressed proliferation in HepG2 and Caco-2 cells. |
| Animal experiment [2]: | |
Animal models | BALB/c male mice |
Preparation Method | CT26 tumors were constructed subcutaneously injecting CT26 cells (5×105 per mouse in a 100mL medium) into 6-week-old BALB/c male mice. Tumor volumes were measured every day. Mice were pooled and randomly divided into four groups with comparable average tumor size. Mice were grouped into control (PBS), Mevalonate (lithium salt), anti-mouse PD-L1 and Mevalonate (lithium salt) plus anti-mouse PD-L1 treatment. PBS or Mevalonate (lithium salt) were treated daily by intraperitoneal injection (100mg/kg), and antimouse PD-L1 treatment was given twice a week by intravenous injection (5mg/kg). Mice were euthanized 14 days after drug treatment or if the tumor volume exceeded 2000mm3 . Mouse tumors tissues were collected for western blot analysis and ELISA assay of tumor cytokines. |
Dosage form | 100mg/kg/day; i.p.; 14 days |
Applications | Mevalonate (lithium salt) enhanced anti-PD-L1 antibody efficacy, upregulated tumor PD-L1 expression, and elevated IFN-γ, IL-2, and TNF-α secretion in CT26 colon cancer-bearing BALB/c mice. |
References: | |
| Cas No. | 2618458-93-6 | SDF | Download SDF |
| 别名 | Mevalonic Acid, MVA, Pentanoic Acid | ||
| Canonical SMILES | O=C(CC(O)(CCO)C)O.[Li] | ||
| 分子式 | C6H11LiO4 | 分子量 | 154.09 |
| 溶解度 | H2O : 100 mg/mL (648.97 mM; Need ultrasonic); DMSO : 50 mg/mL (324.49 mM; Need ultrasonic) | 储存条件 | Store at 2-8°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.4897 mL | 32.4486 mL | 64.8971 mL |
| 5 mM | 1.2979 mL | 6.4897 mL | 12.9794 mL |
| 10 mM | 649 μL | 3.2449 mL | 6.4897 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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