Maraviroc
(Synonyms: 马拉维若,UK-427857; Selzentry; Celsentri) 目录号 : GC15090
马拉韦罗作为第一款CCR5拮抗剂已被批准用于治疗HIV感染，对hERG离子通道的IC50＞10μM。
Cas No.:376348-65-1
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Maraviroc, the first CCR5 antagonist, has been approved for the treatment of HIV infection, IC50 on hERG ion channel＞10μM[1]. Maraviroc also has been viewed as a new therapeutic strategy to treat neuroinflammatory diseases such as multiple sclerosis, Rasmussen encephalitis [2].
Maraviro (3µg/ml for 48 hours) could regulate the release of pro-inflammatory factors related to liver fibrosis in LX-2 cells (a human hepatic stellate cell line). These pro-inflammatory factors led to an increase in the expression levels of cyclin D1 and p21, while the expression of p53 decreases, thereby blocking cell growth in the S phase. Therefore, maraviro may play an important role in the treatment of liver fibrosis[3].
Maraviroc (20mg/kg for 3 days) significantly enhanced tissue preservation and improved neurological function in traumatic brain injury (TBI) mice[4]. Maraviroc treatment (120mg/kg, 200μl, twice/day) also significantly reduced blood and brain viral loads and reduced HIV induced increase in amyloid-beta (Aβ)-42, gamma-secretase activating protein (GSAP), and phospho-Tau in NOD/scid–IL-2Rγc null (NSG) mice, thereby reducing viremia, preserving the BBB and neurons, increasing brain Aβ efflux, and reducing AD-like neuropathologies[5].
[1] Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother. 2005;49(11):4721-32. doi: 10.1128/aac.49.11.4721-4732.2005. PubMed PMID: 16251317.
[2] Martin-Blondel G, Brassat D, Bauer J, Lassmann H, Liblau RS. CCR5 blockade for neuroinflammatory diseases--beyond control of HIV. Nat Rev Neurol. 2016;12(2):95-105. Epub 20160118. doi: 10.1038/nrneurol.2015.248. PubMed PMID: 26782333.
[3] Coppola N, Perna A, Lucariello A, Martini S, Macera M, Carleo MA, et al. Effects of treatment with Maraviroc a CCR5 inhibitor on a human hepatic stellate cell line. J Cell Physiol. 2018;233(8):6224-31. Epub 20180312. doi: 10.1002/jcp.26485. PubMed PMID: 29336497.
[4] Liu XL, Sun DD, Zheng MT, Li XT, Niu HH, Zhang L, et al. Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes. Neural Regen Res. 2023;18(1):141-9. doi:10.4103/1673-5374.344829. PubMed PMID: 35799534.
[5] Bhargavan B, Woollard SM, McMillan JE, Kanmogne GD. CCR5 antagonist reduces HIV-induced amyloidogenesis, tau pathology, neurodegeneration, and blood-brain barrier alterations in HIV-infected hu-PBL-NSG mice. Mol Neurodegener. 2021;16(1):78. Epub 20211122. doi: 10.1186/s13024-021-00500-0. PubMed PMID: 34809709.
马拉韦罗作为第一款CCR5拮抗剂已被批准用于治疗HIV感染，对hERG离子通道的IC50＞10μM[1]。马拉韦罗也被视为治疗神经炎症性疾病如多发性硬化症、拉斯穆森脑炎的新型治疗策略[2]。
马拉韦罗(3µg/ml持续48小时)可以调控LX-2细胞（人肝星状细胞系）中肝纤维化有关的促炎因子的释放，这些促炎因子会导致细胞周期蛋白D1和p21的表达水平增加，p53的表达减少，从而阻滞细胞在S期的生长。因此，马拉韦罗在肝纤维化的治疗中可能发挥重要作用[3]。
马拉韦罗（20mg/kg，持续3天）显著提高了创伤性脑损伤（TBI）小鼠的组织保存并改善了神经功能[4]。马拉韦罗治疗（120mg/kg，200μl，每天两次）也显著降低了NOD/scid–IL-2Rγc null (NSG)小鼠血液和大脑病毒载量以及减少HIV诱导的β淀粉样-42、γ分泌酶激活蛋白(GSAP)和磷酸化Tau的增加，因此减少了病毒血症，保护了血脑屏障和神经元，增加了脑β淀粉样流出并且减少类阿尔茨海默病[5]。
|
Cell experiment [1]: |
|
|
Cell lines |
HeLa P4 C5 cells |
|
Preparation method |
CCR5-expressing HeLa P4 C5 cells were cultured at 37°C under CO2 in DMEM. All seeded cells were treated with different concentrations of maraviroc (5, 10, and 20 µM) added to the cultured cells, and cells were harvested at different time points (2, 6, 12 and 24 h). |
|
Reaction Conditions |
5, 10, and 20µM maraviroc for 2, 6, 12, and 24h |
|
Applications |
In HeLa P4 C5 cells, NF-kB activity was observed after maraviroc treatment. Maraviroc can induce NF-kB activity and that NF-kB targets gene expression by CCR5 binding, since the use of TAK779, a CCR5 inhibitor, blocked NF-kB activation and functionality. |
|
Animal experiment [2]: |
|
|
Animal models |
Female RAG-hu mice |
|
Preparation method |
Female RAG-hu mice were administered with maraviroc(62mg/kg) by oral gavage. Maraviroc was freshly dissolved in distilled water each day prior to oral gavage. |
|
Dosage form |
62 mg/kg/d, oral gavage |
|
Applications |
Oral administration of maraviroc protects humanized mice against vaginal infection. |
|
References: [1] Madrid-Elena N, García-Bermejo ML, Serrano-Villar S, Díaz-de Santiago A, Sastre B, Gutiérrez C, et al. Maraviroc Is Associated with Latent HIV-1 Reactivation through NF-κB Activation in Resting CD4(+) T Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. J Virol. 2018;92(9). Epub 20180413. doi: 10.1128/jvi.01931-17. PubMed PMID: 29444937. [2] Neff CP, Ndolo T, Tandon A, Habu Y, Akkina R. Oral pre-exposure prophylaxis by anti-retrovirals raltegravir and maraviroc protects against HIV-1 vaginal transmission in a humanized mouse model. PLoS One. 2010;5(12):e15257. Epub 20101221. doi: 10.1371/ journal.pone.0015257. PubMed PMID: 21203568. |
|
| Cas No. | 376348-65-1 | SDF | |
| 别名 | 马拉维若,UK-427857; Selzentry; Celsentri | ||
| 化学名 | 4,4-difluoro-N-[(1S)-3-[(1S,5R)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide | ||
| Canonical SMILES | CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C | ||
| 分子式 | C29H41F2N5O | 分子量 | 513.67 |
| 溶解度 | ≥ 25.7mg/mL in DMSO, ≥ 48 mg/mL in EtOH | 储存条件 | Desiccate 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9468 mL | 9.7339 mL | 19.4678 mL |
| 5 mM | 0.3894 mL | 1.9468 mL | 3.8936 mL |
| 10 mM | 0.1947 mL | 0.9734 mL | 1.9468 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。
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet