Maraviroc
别名: UK-427857 中文名称：马拉维若
Maraviroc是一种CCR5拮抗剂，作用于MIP-1α，MIP-1β和RANTES，无细胞试验中IC50分别为3.3 nM，7.2 nM和5.2 nM。Maraviroc可应用于治疗HIV感染。
Maraviroc Chemical Structure
CAS: 376348-65-1
产品质控
批次：
纯度：
99.99%
99.99
常与Maraviroc一起在实验中被使用的化合物
Maraviroc和Pembrolizumab在转移性结直肠癌的1期试验中显示出阳性毒性模式。
在RET细胞-细胞融合测定中，Maraviroc和Leronlimab(PRO-140)共同抑制HIV-1JR-FL包膜介导的膜融合。
Murga JD, et al. Antimicrob Agents Chemother. 2006 Oct;50(10):3289-96.
Maraviroc和Etravirine可用于挽救核苷逆转录酶抑制剂(NRTI)完全耐药的患者。
Vallabhaneni S, et al. J Int AIDS Soc. 2013 Jun 3;16(1):18449.
Maraviroc和Vicriviroc可减少免疫功能正常小鼠的前列腺癌细胞向骨骼、大脑和内脏的转移。
Maraviroc和Tenofovir对孕激素受体B(PR-B)的激活具有背景特异性影响。
Enfield K, et al. Biochem Biophys Res Commun. 2020 Dec 17;533(4):1027-1033.
Maraviroc相关产品
| 相关靶点 | CCR1 CCR2 CCR3 CCR4 CCR5 CCR8 CCL | 点击展开 |
|---|---|---|
| 相关产品 | Cenicriviroc Vicriviroc Malate Adaptavir (DAPTA) ZK756326 2HCl SB-297006 INCB3344 RS102895 Vicriviroc maleate AZD2098 | 点击展开 |
| 相关化合物库 | 抗感染化合物库 抗生素化合物库 抗病毒化合物库 抗寄生虫药物库 肠道微生物代谢物库 | 点击展开 |
相关信号通路图
细胞实验数据示例
| 细胞系 | 实验类型 | 给药浓度 | 孵育时间 | 活性描述 | 文献信息 |
|---|---|---|---|---|---|
| TZM-bl | Function assay | 48 hrs | Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 YU2-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00043 μM. | 24563723 | |
| TZM-bl | Function assay | 48 hrs | Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 MGC26-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.00037 μM. | 24563723 | |
| TZM-bl | Function assay | 3 days | Inhibition of CCR5 in human TZM-bl cells infected with HIV1 Bal R5 assessed as antiviral activity by measuring reduction in viral infection pre-incubated with cells followed by viral infection measured after 3 days by luciferase reporter gene assay, IC50 = 0.0002 μM. | 28082070 | |
| HeLa-P4 | Function assay | 20 hrs | 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 = 0.0002 μM. | 21128663 | |
| PM1 | Antiviral assay | 5 days | Antiviral activity against CCR5-dependent HIV1 Ba-L infected in human PM1 cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.001 μM. | 30234300 | |
| SupT1 | Antiviral assay | 48 hrs | Antiviral activity against HIV-1 infected in human SupT1 cells assessed as inhibition of viral infectivity after 48 hrs by luciferase reporter gene assay, IC50 = 0.0011 μM. | 24316669 | |
| TZM-bl | Function assay | 48 hrs | Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 92RW-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.0013 μM. | 24563723 | |
| CHO | Function assay | 2 hrs | Displacement of [128I]RANTES from human CCR5 receptor coexpressed with Galphai6 in CHO cells after 2 hrs by scintillation counting, IC50 = 0.0014 μM. | 20137937 | |
| TZM-bl | Function assay | 48 hrs | Antagonist activity against CCR5 receptor in human TZM-bl cells assessed as inhibition of HIV-1 JR-FL-induced cell-cell fusion between viral envelope protein expressing human HEK293 cells to TZM-bl cells after 48 hrs by luciferase reporter gene assay, IC50 = 0.0016 μM. | 24563723 | |
| HOS | Antiviral assay | 5 days | Antiviral activity against CCR5-dependent HIV1 Ba-L infected in human HOS cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.0019 μM. | 30234300 | |
| MOLT4 | Function assay | 15 mins | Antagonist activity at CCR5 in Gqi5 transfected human MOLT4 cells assessed as inhibition of RANTES-stimulated Ca2+ influx preincubated for 15 mins followed by DAMGO challenge, IC50 = 0.0022 μM. | 23682308 | |
| JC53-BL | Antiviral assay | 3 days | Antiviral activity against CCR5-tropic recombinant HIV1 NLBal virus infected in JC53-BL cells assessed as inhibition of viral replication after 3 days by luciferase reporter gene assay, IC50 = 0.0028 μM. | 20137937 | |
| JC53-BL | Antiviral assay | 3 days | Antiviral activity against HIV1 NL4-3 infected in human JC53-BL cells assessed as luciferase activity after 3 days post infection, IC50 = 0.003 μM. | 20417098 | |
| HOS | Antiviral assay | 5 days | Antiviral activity against CCR5-dependent HIV1 SF162 infected in human HOS cells assessed as reduction in virus infection measured after 5 days by luciferase reporter gene assay, IC50 = 0.0047 μM. | 30234300 | |
| NIH/3T3 | Function assay | 1 hr | Displacement of [125I]-RANTES from CCR5 in mouse NIH/3T3 cells after 1 hr, IC50 = 0.0052 μM. | 29425816 | |
| SupT1 | Antiviral assay | 48 hrs | Antiviral activity against HIV1 infected in human SupT1 cells exposed to supernatant from HIV1 infected human 293T cells incubated for 48 hrs by firefly luciferase assay based single-cycle HIV1 replication assay, IC50 = 0.0055 μM. | 25638498 | |
| TZM-bl | Antiviral assay | 48 hrs | Antiviral activity against CCR5-dependent HIV1 SF162 infected in human TZM-bl cells assessed as reduction in virus infection measured after 48 hrs post infection by luciferase reporter gene assay, IC50 = 0.0067 μM. | 30234300 | |
| HEK293 | Function assay | 10 mins | Antagonist activity at CCR5 (unknown origin) expressed in HEK293 cells co-expressing Galpha16 assessed as inhibition of RANTES-induced calcium flux preincubated for 10 mins followed by RANTES addition by fluo-4AM-based fluorescence assay, IC50 = 0.008 μM. | 30234300 | |
| CHO | Function assay | 10 mins | Antagonist activity against CCR5 (unknown origin) expressed in CHO cells co-expressing Galpha16 incubated for 10 mins assessed as inhibition of RANTES-induced calcium mobilization, IC50 = 0.0131 μM. | 25638498 | |
| CHO | Function assay | 10 mins | Inhibition of CCR5 (unknown origin) expressed in CHO cells assessed as inhibition of RANTES-induced intracellular Ca2+ mobilization after 10 mins by Fluo-4 AM staining-based fluorescence assay, IC50 = 0.02543 μM. | 24316669 | |
| HEK293 | Function assay | 1.5 mins | 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 | Function assay | Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay, IC50 = 0.0002 μM. | 19171484 | ||
| PM1 | Antiviral assay | Antiviral activity against HIV1 Bal infected in human PM1 cells assessed as inhibition of viral replication, IC90 = 0.0007 μM. | 19171484 | ||
| HOS | Antiviral assay | Antiviral activity against HIV1 Ba-L infected in HOS cells assessed as inhibition of viral infection, IC50 = 0.002 μM. | 19664920 | ||
| A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
| NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells | 29435139 | ||
| Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells | 29435139 | ||
| RD | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells | 29435139 | ||
| NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells | 29435139 | ||
| SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells | 29435139 | ||
| SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells | 29435139 | ||
| Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
| 点击查看更多细胞系数据 | |||||
生物活性
| 产品描述 | Maraviroc是一种CCR5拮抗剂，作用于MIP-1α，MIP-1β和RANTES，无细胞试验中IC50分别为3.3 nM，7.2 nM和5.2 nM。Maraviroc可应用于治疗HIV感染。 | ||||||||
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| 靶点 |
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| 体外研究(In Vitro) | ||||
| 体外研究活性 | Maraviroc 抑制MIP-1β刺激的γ-S-GTP 结合到HEK-293细胞膜上, 说明 Maraviroc 可抑制GDP-GTP 在CCR5/G 蛋白复合体上交换的趋化因子依赖性刺激。Maraviroc 也抑制趋化因子诱导的细胞内钙重新分配的下游事件，作用于 MIP-1β, MIP-1α 和RANTES时，IC50s 为 7 到 30 nM。在相同实验中, Maraviroc 即使浓度高达10 μM，也不会触发细胞内钙释放，说明Maraviroc 缺乏 CCR5兴奋剂活性。与此相应地, Maraviroc也不能诱导CCR5内化。Maraviroc 低纳摩尔浓度时，也有效作用于 HIV-1 Ba-L。 Maraviroc 抑制所有 200种假型病毒，平均IC90为13.7 nM。[1] 在浓度高达其IC50的1000倍时，Maraviroc对其他chemokine receptors (CCR1, 2, 3, 4, 7, 8; CXCR1, 2) 没有相关临床程度的抑制作用[3]. |
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| 激酶实验 | 趋化因子与 CCR5结合的抑制作用 | |||
| 使用稳定表达受体或膜及其制品的昆虫HEK-293细胞测量125I-标记的 MIP-1α, MIP-1β,和 RANTES 与CCR5结合情况。细胞按2 × 106 个细胞/ml的密度再悬浮在结合buffer (50 mM HEPES 含1 mM CaCl2, 5 mM MgCl2, 和 0.5%牛血清蛋白[BSA]，调节pH为 7.4) 中。为了制备膜，PBS冲洗的细胞再悬浮在 裂解 buffer (20 mM HEPES, 1 mM CaCl2, 1 片 COMPLETE /50 mL, pH 7.4)中，然后在Polytron 手持匀浆器中搅匀, 在40,000× g下超速离心30分钟，再悬浮在 结合 buffer中，蛋白浓度为0.25 mg/mL (96-孔板的每孔中含 12.5 μg 膜蛋白)。制备125I-放射性标记的 MIP-1α, MIP-1β, 和 RANTES ，在 结合 buffer中稀释，终浓度为400 pM。每孔加入Maraviroc 稀释液，终体积为100 μL, 实验板温育1小时, 通过预阻断和冲洗的 Unifilter 板过滤，计数，烘干过夜。 | ||||
| 细胞实验 | 细胞系 | PHA刺激的PBMC或PM-1细胞 | ||
| 浓度 | 0-1 μM | |||
| 孵育时间 | 5天或7天 | |||
| 方法 | 在24孔组织培养板上进行药物敏感性试验。在DMSO中制备重复的8点连续稀释Maraviroc，实验中DMSO终浓度为 0.1% (vol/vol)。PHA刺激的PBMC或PM-1细胞感染细胞，在37oC下进行1小时。细胞随后稀释一次，3.6 × 105 PBMC 或2.0 × 105 PM-1细胞加到含稀释 Maraviroc的每孔中。实验板在37oC下在含5% CO2 (vol/vol) 环境下温育5天（实验室适应株）或7天（原始分离株）。所有实验中含Saquinavir (一种 HIV-1 蛋白酶抑制剂) 和RANTES。 |
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| 实验图片 | 检测方法 | 检测指标 | 实验图片 | PMID |
| Western blot | cleaved caspase-3 / cleaved caspase-9 / cleaved PARP / XIAP / Survivin / c-IAP1 / c-IAP2 / Bax / Bad / Bcl2 / Bcl-xl |
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28469959 | |
| 体内研究(In Vivo) | ||
| 体内研究活性 | Maraviroc 作用于大鼠的半衰期为 0.9小时，作用于犬类的半衰期为2.3小时。 随后Maraviroc按2 mg/kg剂量口服给药犬类，1.5小时后达到 Cmax(256 ng/ml)，生物有效性为40%。Maraviroc作用于大鼠，大约 30% 给药剂量从肠道吸收。[1]雌性RAG-hu小鼠阴道内部加入 Maraviroc凝胶后，再阴道注入HIV-1 1小时。Maraviroc 凝胶处理的小鼠完全免受HIV-1 感染，而安慰剂处理的小鼠则全部感染。说明Maraviroc 完全保护小鼠免受 HIV-1 感染。在安慰剂处理的病毒感染小鼠内，CD4 T细胞明显下降，而Maraviroc 凝胶处理小鼠中水平稳定。[2] |
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| 动物实验 | Animal Models | 人性化的 BALB/c-Rag2−/−γc−/−和BALB/c-Rag1−/−γc−/− (RAG-hu)小鼠 |
| Dosages | ~64 μg | |
| Administration | 25μL凝胶配方小心地加到小鼠的阴道穹窿中。 | |
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
|---|---|---|---|---|---|
| NCT04966429 | Recruiting | Post Stroke Cognitive Impairment |
Tel-Aviv Sourasky Medical Center|Hadassah Medical Organization|Soroka University Medical Center |
May 1 2021 | Phase 2 |
| NCT04710199 | Completed | Virus Diseases |
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla |
February 23 2021 | Phase 2 |
| NCT02881762 | Completed | Hepatitis C|Human Immunodeficiency Virus |
University of Maryland Baltimore|ViiV Healthcare |
June 1 2017 | Phase 4 |
| NCT02778204 | Completed | HIV Infections |
National Institute of Allergy and Infectious Diseases (NIAID)|Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)|ViiV Healthcare|GlaxoSmithKline |
June 5 2017 | Phase 1 |
| NCT02741323 | Completed | HIV Infections|Kidney Diseases |
National Institute of Allergy and Infectious Diseases (NIAID) |
January 1 2017 | Phase 2 |
化学信息&溶解度
| 分子量 | 513.67 | 分子式 | C29H41F2N5O |
| CAS号 | 376348-65-1 | SDF | Download Maraviroc SDF |
| Smiles | CC1=NN=C(N1C2CC3CCC(C2)N3CCC(C4=CC=CC=C4)NC(=O)C5CCC(CC5)(F)F)C(C)C | ||
| 储存条件(自收到货起) | |||
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体外溶解度 |
DMSO : 100 mg/mL ( (194.67 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO) Ethanol : 100 mg/mL (194.67 mM) Water : Insoluble |
摩尔浓度计算器 |
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体内溶解度 现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂 |
动物体内配方计算器 | ||||
实验计算
动物体内配方计算器（澄清溶液）
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）
mg/kg
g
μL
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Selleck为您提供正确的澄清溶液配方）
% DMSO
%
% Tween 80
% ddH2O
%DMSO
%
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，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；
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 ddH2O，混匀澄清。
体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。
注意：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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常见问题及建议解决方法
问题 1:
What’s the vehicle do you recommend to dissolve the compound for in vivo experiments?
回答：
S2003 Maraviroc can be dissolved in 5% DMSO/castor oil at 62 mg/ml as suspension for oral administration. As to a clear solution for injection, following three vehicles at 10mg/ml will help: 1. 2% DMSO/castor oil; 2. 2%DMSO/sunflower oil; 3. 2%DMSO/30%PEG 300/ddH2O.
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