Geranylgeranyl Pyrophosphate (ammonium salt)
(Synonyms: GGPP) 目录号 : GC43747An isoprenoid important for post-translational modifications of GTPases
Cas No.:313263-08-0
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Geranylgeranyl pyrophosphate is an intermediate in the HMG-CoA reductase pathway derived directly from farnesyl pyrophosphate and used in the biosynthesis of terpenes and terpenoids.[1] It is also serves as a substrate in the prenylation of a variety of critical intracellular proteins including small GTPases.[2] This post-translational modification is necessary for correct localization of proteins to intracellular membranes for proper functionality and has become a focus of anticancer drug discovery.[3][4]
戊二烯基焦磷酸是HMG-CoA还原酶途径中的中间产物，直接来自于法尼酰基焦磷酸，用于萜类和萜类化合物的生物合成。[1] 它还作为底物参与了多种重要细胞内蛋白质的预酰化，包括小GTP酶。[2] 这种翻译后修饰对蛋白质定位到细胞内膜以获得正确的功能性是必要的，并成为抗癌药物发现的焦点。[3][4]
Reference:
[1]. Vance, D.E. Cholesterol and related derivatives. Biochemistry 2nd ed., 725-748 (1988).
[2]. McTaggart, S.J. Isoprenylated proteins. Cell Mol.Life Sci. 63(3), 255-267 (2006).
[3]. Baron, R.A., and Seabra, M.C. Rab geranylgeranylation occurs preferentially via the pre-formed REP-RGGT complex and is regulated by geranylgeranyl pyrophosphate. Biochemistry Journal 415(1), 67-75 (2008).
[4]. Maynor, M., Scott, S.A., Rickert, E.L., et al. Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate analogs. Bioorganic & Medicinal Chemistry Letters 18(6), 1889-1892 (2008).
| Cas No. | 313263-08-0 | SDF | |
| 别名 | GGPP | ||
| 化学名 | P-[(2E,6E,10E)-3,7,11,15-tetramethyl-2,6,10,14-hexadecatetraen-1-yl] ester-diphosphoric acid, triammonium salt | ||
| Canonical SMILES | C/C(CC/C=C(C)\C)=C\CC/C(C)=C/CC/C(C)=C/COP(OP([O-])([O-])=O)([O-])=O.[NH4+].[NH4+].[NH4+] | ||
| 分子式 | C20H33O7P2•3NH4 | 分子量 | 501.5 |
| 溶解度 | Methanol:10mM NH4OH (70:30): 1 mg/mL | 储存条件 | Store at -20°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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.994 mL | 9.9701 mL | 19.9402 mL |
| 5 mM | 0.3988 mL | 1.994 mL | 3.988 mL |
| 10 mM | 0.1994 mL | 0.997 mL | 1.994 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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Statins directly suppress cytokine production in murine intraepithelial lymphocytes
Cytokine 2013 Feb;61(2):540-5.PMID:23290865DOI:10.1016/j.cyto.2012.12.006.
Statins, inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, are known not only as cholesterol-lowering agents but also as anti-inflammatory mediators. However, their regulatory effect on intestinal mucosal immunity remains unclear. The present study examined the possible direct effects of statin on intestinal intraepithelial lymphocytes (IELs), the front line cells of the intestinal mucosal immune system. Murine IELs were isolated from the small intestines of C57BL/6 mice. IELs activated with anti-CD3/CD28 monoclonal antibodies produced interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-4 in significant numbers; however, they did not produce IL-5. Both simvastatin and lovastatin suppressed IEL production of IFN-γ, TNF-α, IL-2, and IL-4 in a dose-dependent manner, whereas 48-h treatment with high concentrations (5 × 10(-5)M) of simvastatin and lovastatin did not affect the number of IELs. The suppressive effect of the simvastatin was significantly restored by the addition of mevalonate, farnesyl pyrophosphate ammonium salt, and Geranylgeranyl Pyrophosphate ammonium salt, which are downstream metabolites of HMG-CoA. These findings suggest that statins have direct suppressive effects on the production of T helper 1-cytokines and IL-4 in IELs; these effects are associated with inhibition of the mevalonate pathway to some extent.
The impact of statins on FGF-2-stimulated human umbilical vein endothelial cells
Postgrad Med 2014 Jan;126(1):118-28.PMID:24393759DOI:10.3810/pgm.2014.01.2732.
Aim: To determine the effects of different types of statins on proliferative and migrative behaviors of basic fibroblastic growth factor (FGF)-2-stimulated endothelial cells. Materials and methods: Human umbilical vein endothelial cells (HUVECs) were isolated and cultured. Groups were arranged in order to observe the impact of each individual substance alone, or under stimulation with statin on FGF-2-stimulated endothelial cells. Endothelial cells were stimulated with human growth factor (HGF), statins, methyl-β-cyclodextrin (β-MCD), and either farnesyl pyrophosphate (FPP) ammonium salt, or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferation analyses were performed 48 hours after stimulation and gaps between migration borders were used in migration analyses. Results: The statins showed significant antiproliferative and anti-migrative effects and inhibited the proliferative behavior of FGF-2. However, endothelial cell proliferation and migration were significantly increased after mevalonate co-incubation. Experiments with β-MCD indicated that the destruction of lipid rafts had a negative impact on the action of FGF-2. Stimulation of statin-incubated cells with FPP had no additional effect on proliferation or migration. Notably, although FGF-2 exerted a pro-migrative effect, the effect was not shown in the FPP + FGF-2 group. The anti-migrative actions of statins along with disruption of membrane integrity were reversed by the addition of GGPP. Conclusion: The angiogenic effect of FGF-2 is suppressed through inhibition of the intracellular cholesterol biosynthesis via statins. Inhibitory effects of statins on FGF-2-stimulated HUVECs were observed to result from both the inhibition of isoprenylation and the destruction of lipid rafts on the cell membrane.
Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells
Toxicol Lett 2010 Dec 15;199(3):277-87.PMID:20883752DOI:10.1016/j.toxlet.2010.09.010.
Recent studies have suggested that oxidative stress may play a role in the cytotoxic activity of statins against cancer cells. The objective of this study was to elucidate the role of oxidative stress in the cytotoxicity of simvastatin in murine CT26 colon carcinoma cells and B16BL6 melanoma cells. We found that CT26 cells were more sensitive to simvastatin than B16BL16 cells. Interestingly, exposure to simvastatin causes significant apoptotic cell death and perturbations in parameters indicative of oxidative stress in CT26 cells. Moreover, the increase in oxidative stress parameters and cell death were suppressed by isoprenoids including mevalonolactone, farnesyl pyrophosphate ammonium salt, Geranylgeranyl Pyrophosphate ammonium salt, and coenzyme Q10, and by antioxidants including N-acetyl cysteine, reduced glutathione, superoxide dismutases (SOD), and catalase (CAT) alone or in combination, but were promoted by an inhibitor of glutathione synthesis, L-buthionine-sulfoximine. The signaling pathway induced by simvastatin breaks down the antioxidant defense system by suppressing the expression of reactive oxygen species scavengers, particularly Mn-SOD, CAT, GPx1, and SESN 3, thereby inducing oxidative stress and apoptotic cell death. Collectively, our results demonstrate that simvastatin induces colon cancer cell death at least in part by increasing intracellular oxidative stress and inducing apoptosis.
The effects of different types of statins on proliferation and migration of HGF-induced Human Umbilical Vein Endothelial Cells (HUVECs)
Eur Rev Med Pharmacol Sci 2013 Nov;17(21):2874-83.PMID:24254555doi
Background and aim: Statins are HMG-CoA reductase inhibitors within the framework of cholesterol biosynthesis and used to lower the low-density lipoprotein (LDL). There are other aspects of statins can deploy a protective effect, even without the LDL's lowering. The aim of this study is to investigate the effects of different type of statins on proliferative and migrative behaviors of Hepatocyte Growth Factor (HGF) induced human umbilical vein endothelial cells (HUVECs). Materials and methods: Human umbilical vein endothelial cells were isolated and cultured. Groups were designed in order to observe the effects of every individual substance. HUVECs were stimulated with HGF, statins and farnesylpyrophosphat ammonium salt (FPP) or geranylgeranyl-pyrophosphate (GGPP), respectively. Cell proliferations were counted 48 hours after initial stimuli and distances between migration fronts were used in migration analyses. Results: All types of statins showed significant anti-migrative and anti-proliferative characters. Simvastatin and fluvastatin but not cerivastatin, were able to inhibit the HGF-depending migration and showed a significant effect on the inhibition of the isoprenylation (GGPP). Only simvastatin influenced the HGF-depending migration via inhibiting the isoprenylation process through GGPP. Cerivastatin significantly decreased the proliferation and Fluvastatin significantly enhanced the migration behaviors of HUVECs when they were co-incubated with methyl-8-cyclodextrin (MCD). Conclusions: Statins countermand the proproliferative and as well as the promigrative effect of HGF on HUVECs. The mechanisms which provoke this effect are dependent on the type of statin. Direct interactions of statins with lipid rafts play a significant role in the endothelial cell mechanisms.
Identification of a selective agonist for liver X receptor α (LXRα) via screening of a synthetic compound library
J Biomol Screen 2014 Apr;19(4):566-74.PMID:24334278DOI:10.1177/1087057113516004.
Liver X receptor α (LXRα) plays an important role in reverse cholesterol transport (RCT), and activation of LXRα could reduce atherosclerosis. In the present study, we developed a screening method to identify new potential LXRα agonists using an LXRα-GAL4 chimera reporter assay. A novel analogue of N,N-disubstituted 2,8-diazaspiro[4.5]decane, IMB-151, was identified as an LXRα agonist by using this method. IMB-151 showed a significant activation effect on LXRα, with an EC50 value of 1.47 µM. IMB-151 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. The upregulating effects of IMB-151 on ABCA1 and ABCG1 markedly decreased when coincubated with Geranylgeranyl Pyrophosphate (GGPP) ammonium salt or LXRα small interfering RNA (siRNA). Our data indicated that the upregulation of ABCA1 and ABCG1 by IMB-151 depended on activation of LXRα. Moreover, IMB-151 significantly reduced cellular lipid accumulation and increased cholesterol efflux in RAW264.7 macrophages. Interestingly, IMB-151 slightly increased sterol response element binding protein 1c (SREBP-1c) protein expression levels in HepG2 cells compared with TO901317, and this indicated that IMB-151 might have less lipogenesis side effect in vivo. These results suggested that IMB-151 was identified as a selective agonist for LXRα by using a screening method and could be used as a potential antiatherosclerotic lead compound in the future.