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Maraviroc

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Chemical Structure| 376348-65-1 同义名 : 马拉维若 ;UK-427857
CAS号 : 376348-65-1
货号 : A330828
分子式 : C29H41F2N5O
纯度 : 99%+
分子量 : 513.666
MDL号 : MFCD13188530
存储条件：

粉末 Keep in dark place,Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(97.34 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

无水乙醇: 6 mg/mL(11.68 mM)，配合低频超声助溶，注意：无水乙醇开封后，易挥发，也会吸收空气中的水分，导致溶解能力下降，请避免使用开封较久的乙醇
动物实验配方：

IP 2% DMSO+2% Tween80+30% PEG300+water 7 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • CCR

    MIP-1β, IC50:5.2 nM

    MIP-1α, IC50:3.3 nM
描述 Maraviroc is a reversible antagonist of C-C chemokine receptor type 5 (CCR5), which inhibits the interaction between CCR5 with the envelop glycoprotein gp120 of human immunodeficiency virus-1 (HIV-1), thus blocking HIV-1 entry into cells[6]. The overall in vitro IC50 of maraviroc ranges from 0.1 to 4.5 nM[7]. Incubation with maraviroc-contained medium at the concentration of 0.1 μM for 48 hours induced CCR5 surface expression on activated T cells. Moreover, 24-hour treatment of 1 μM to 100 μM maraviroc inhibited T cell migration induced by various chemokines. T cell proliferation was also shown to be inhibited after 72-hour incubation with 100 μM maraviroc[8]. A study in female RAG-hu mice showed that 5 mM maraviroc, which was applied into the vaginal vault of mice one hour before viral challenge, fully prevented HIV-1 vaginal transmission[9]. Mice with diet-induced hepatocellular carcinoma showed reduced liver fibrosis, lower levels of liver injury markers, and decreased proliferation index with the treatment of 300 mg/L maraviroc added in drinking water for 16 weeks[10]. A phase 2 trial reported that 300 mg/kg maraviroc twice daily decreased the viral loads by 1.6log10 copies/mL in asymptomatic HIV-1-infected patients[6].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
CHO cells Function assay 2 h Displacement of [128I]RANTES from human CCR5 receptor coexpressed with Galphai6 in CHO cells after 2 hrs by scintillation counting, IC50=1.4 nM 20137937
HEK293 cells Function assay Inhibition of human MATE1-mediated ASP+ uptake expressed in HEK293 cells after 1.5 mins by fluorescence assay, IC50=17.3 Μm 23241029
HeLa-P4 cells Function assay 20 days Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay, IC50=0.2 nM 21128663
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT02519777 HIV Infections Phase 4 Active, not recruiting November 30, 2020 -
NCT02333045 HIV Not Applicable Terminated(Minimal efficacy of... 展开 >> maraviroc alone was found in preliminary data analysis of another study.) 收起 << - United States, Georgia ... 展开 >> Grady Memorial Hospital Atlanta, Georgia, United States, 30303 Grady Infectious Diseases Clinic (Ponce Clinic) Atlanta, Georgia, United States, 30308 收起 <<
NCT00925756 HIV Infections Phase 4 Completed - United States, California ... 展开 >> University Southern California Los Angeles, California, United States, 90033 University California San Diego San Diego, California, United States, 92103 Harbor-UCLA Torrance, California, United States, 90502 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.19mL

9.73mL

1.95mL

0.97mL

19.47mL

3.89mL

1.95mL
参考文献

[1]Neff CP, Kurisu T, et al. A topical microbicide gel formulation of CCR5 antagonist maraviroc prevents HIV-1 vaginal transmission in humanized RAG-hu mice. PLoS One. 2011;6(6):e20209.

[2]Dorr P, Westby 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 Nov;49(11):4721-32.

[3]Mencarelli A, Graziosi L, et al. CCR5 Antagonism by Maraviroc Reduces the Potential for Gastric Cancer Cell Dissemination. Transl Oncol. 2013 Dec 1;6(6):784-93. eCollection 2013 Dec 1.

[4]Nayak SU, Cicalese S, et al. Chemokine CCR5 and cocaine interactions in the brain: Cocaine enhances mesolimbic CCR5 mRNA levels and produces place preference and locomotor activation that are reduced by a CCR5 antagonist. Brain Behav Immun. 2020 Jan;83:288-292.

[5]UK-427857

[6]Woollard SM, Kanmogne GD. Maraviroc: a review of its use in HIV infection and beyond. Drug Des Devel Ther. 2015 Oct 1;9:5447-68.

[7]Dorr P, Westby M, Dobbs S, Griffin P, Irvine B, Macartney M, Mori J, Rickett G, Smith-Burchnell C, Napier C, Webster R, Armour D, Price D, Stammen B, Wood A, Perros M. 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 Nov;49(11):4721-32.

[8]Arberas H, Guardo AC, Bargalló ME, Maleno MJ, Calvo M, Blanco JL, García F, Gatell JM, Plana M. In vitro effects of the CCR5 inhibitor maraviroc on human T cell function. J Antimicrob Chemother. 2013 Mar;68(3):577-86.

[9]Neff CP, Kurisu T, Ndolo T, Fox K, Akkina R. A topical microbicide gel formulation of CCR5 antagonist maraviroc prevents HIV-1 vaginal transmission in humanized RAG-hu mice. PLoS One. 2011;6(6):e20209.

[10]Ochoa-Callejero L, Pérez-Martínez L, Rubio-Mediavilla S, Oteo JA, Martínez A, Blanco JR. Maraviroc, a CCR5 antagonist, prevents development of hepatocellular carcinoma in a mouse model. PLoS One. 2013;8(1):e53992.