Raltegravir (MK-0518)

目录号:S2005 中文名称:拉替拉韦,雷特格韦

仅限科研使用

Raltegravir (MK-0518)是一种有效的integrase (IN)抑制剂,作用于WT和S217Q PFV IN,在无细胞试验中IC50分别为90 nM和40 nM。它对HIV-1 IN的选择性比对其他相关Mg2+依赖性酶要高1000倍以上,如HCV聚合酶、HIV反转录酶、HIV RNaseH、人类α-, β-, γ-聚合酶。

Raltegravir (MK-0518) Chemical Structure

CAS: 518048-05-0

规格 价格 库存 购买数量
10mM (1mL in DMSO) RMB 1722.95 现货
RMB 983.46 现货
RMB 5494.35 现货
大包装 有超大折扣

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客户使用Selleck生产的Raltegravir (MK-0518)发表文献53篇:

产品安全说明书

Integrase抑制剂选择性比较

相关Integrase产品

生物活性

产品描述 Raltegravir (MK-0518)是一种有效的integrase (IN)抑制剂,作用于WT和S217Q PFV IN,在无细胞试验中IC50分别为90 nM和40 nM。它对HIV-1 IN的选择性比对其他相关Mg2+依赖性酶要高1000倍以上,如HCV聚合酶、HIV反转录酶、HIV RNaseH、人类α-, β-, γ-聚合酶。
特性 Raltegravir 是第一个被批准的人类免疫缺陷病毒1型(HIV-1)整合酶抑制剂。
靶点
Integrase (S217Q PFV) [1]
(Cell-free assay)
Integrase (WT PFV) [1]
(Cell-free assay)
40 nM 90 nM
体外研究

PFV整合携带S217H替换的IN,之后对 Raltegravir 的敏感性降低10倍,IC50为900 nM。PFV IN 具有10% WT 活性,且被Raltegravir抑制,IC50为200 nM,说明与 WT IN相比,对整合酶(IN)链转移抑制剂(INSTI)的敏感性降低约2倍。S217Q PFV IN 对 Raltegravir的敏感性至少与WT 酶相似。[1] Raltegravir由葡萄糖醛酸化,而不是肝脏代谢而来。Raltegravir 在体外作用于人类T 淋巴细胞培养物,有效作用于HIV-1,抑制达95%时浓度为31±20 nM。Raltegravir作用于 CEMx174细胞,也有效作用于HIV-2,IC95为6 nM。Raltegravir 代谢主要通过葡萄糖醛酸化。葡萄糖醛酸化酶的强诱导剂UGT1A1显著降低 Raltegravir 浓度。Raltegravir 微弱抑制肝细胞色素 P450。Raltegravir不会诱导 CYP3A4 RNA 表达或 CYP3A4依赖的睾丸激素 6-β-羟化酶活性。[2]在镁和钙存在时,Raltegravir细胞扩散性降低。[3]Raltegravir 和相关的HIV-1整合酶 (IN) 链转移抑制剂 (INSTIs) 高效阻断病毒复制。[4] Raltegravir 作用于急性感染人类淋巴 CD4+ T细胞系MT-4和 CEMx174, 高效抑制SIVmac251复制,EC90处于低纳摩尔范围。[5]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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MT-4 NVH5dYMxSW62aY\pdoFtKGG|c3H5 M4Hse2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JJZme2mldXzhdkB{fG:vYYTpeIl{KH[rcoXzJGcueHOndXTveJlx\WRiSIXtZY4hcW2vdX7v[IVncWOrZX7jfUB3cXK3czDpcoZm[3SnZDDpckBpfW2jbjDNWE01KGOnbHzzJIF{e2W|c3XkJIF{KGmwaHnibZRqd25ib3[geolz[WxicnXwcIlk[XSrb36sJGVEPTBiPTCwMlAxOiEQvF2u NYPyTlhtRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUixOlA2OjFpPkG4NVYxPTJzPD;hQi=>
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MT-2 NV;IU2U3SW62aY\pdoFtKGG|c3H5 M1jDW2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGhKXjFiM1KgbY5n\WO2ZXSgbY4hcHWvYX6gUXQuOiClZXzsd{BjgSC2d3:g[o9t\CCmaXz1eIlwdiCvZYToc4QhcW5icILld4Vv[2Vib3[gNVAmKE[EUzygSWM2OCB;IECuNFA{KM7:TT6= NGnYTHI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zOUGwOFAyOCd-MUmxNFQxOTB:L3G+
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MT4 MlfYRY51cX[rcnHsJIF{e2G7 NXGyeId2SW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhUEmYMTCzRkBqdm[nY4Tl[EBqdiCqdX3hckBOXDRiY3XscJMh[XO|ZYPz[YQh[XNiaX7obYJqfGmxbjDv[kB3cXK3cz3pcoR2[2WmIHP5eI9x[XSqaXOg[YZn\WO2IHL5JG1VXCCjc4PhfUwhTUN3MDC9JFAvODB4IN88UU4> M33xVlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwO|E5Lz5{NEmwNFcyQDxxYU6=
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MT4 NVfXSnJXSW62aY\pdoFtKGG|c3H5 M3L2OmFvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JGh2dWGwIHntcZVvd2SnZnnjbYVv[3lidnnyeZMhOSB|QjDpcoZm[3SnZDDpckBpfW2jbjDNWFQh[2WubIOgZZN{\XO|ZXSgZZMhcW6qaXLpeIlwdiCxZjD2bZJ2eyCrbnT1Z4VlKGO7dH;wZZRpcWNiZX\m[YN1NCCHQ{WwJF0hOC5yME[xJO69VS5? NFvrSIY9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MES3PVIxPid-MkC0O|kzODZ:L3G+
MT4 NXPpOFcxTnWwY4Tpc44h[XO|YYm= NWTmSoVoOSCqch?= NHT1NXdKdmirYnn0bY9vKG:oIIfpcIQhfHmyZTDITXYyKDOEIHnu[oVkfGWmIHnuJIh2dWGwIF3UOEBk\WyuczD1d4lv\yClZXzsd{BxemVvaX7jeYJifGWmIIfpeIgh[2:vcH;1coQh\m:{IEGgbJIhdWWjc4Xy[YQhPCCmYYnzJJBwe3RidnnyZYwhcW6oZXP0bY9vKGK7IF3UWEBie3OjeTygTWM2OCB;IECuNFA3OiEQvF2u MXi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOjl4M{GzOUc,OjJ7NkOxN|U9N2F-
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U373-MAGI NY\tRphtSW62aY\pdoFtKGG|c3H5 M3Lt[|UxKG:{IEGwNEBvVQ>? M2P0V|czKGi{cx?= NIm1RWdCdnSrdnnyZYwh[WO2aY\peJkh[WejaX7zeEBXW1ZvRzDwd4V2\G:2eYDl[EBJUVZvMTDOUFQuOyCrbn\lZ5Rm\CCrbjDoeY1idiCXM{ezMW1CT0liY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJIdi\yCuZY\lcEBifCB3MDDvdkAyODBibl2gcYVie3W{ZXSgZZQhPzJiaILzJJBwe3RiaX7m[YN1cW:wIHL5JJFRS1JibXX0bI9l MoX5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjdzMUeyOlAoRjJ5MUG3NlYxRC:jPh?=
U373-MAGI M{\TTWFvfGm4aYLhcEBie3OjeR?= MoHIOVAhd3JiMUCwJI5O NHvneWc4OiCqcoO= NWH1V2MySW62aY\pdoFtKGGldHn2bZR6KGGpYXnud5QhXlOYLVegdJNmfWSxdInw[YQhUEmYLUGgUmw1NTNiaX7m[YN1\WRiaX6gbJVu[W5iVUO3N{1OSUeLIHPlcIx{KGG|c3Xzd4VlKGG|IILl[JVkfGmxbjDpckBWPS2pYXegcIV3\WxiYYSgOVAhd3JiMUCwJI5OKG2nYYP1doVlKGG2IEeyJIhzeyCyb4P0JIlv\mWldHnvckBjgSCzUFPSJI1mfGixZB?= NVnEZoJJRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkexNVczPjBpPkK3NVE4OjZyPD;hQi=>
MT2 MU\BcpRqfmm{YXygZZN{[Xl? MoXsNUB2VQ>? MVuzNEBpenN? M2[3O2FvfGm4aYLhcEBi[3Srdnn0fUBi\2GrboP0JJdqdGRvdInw[UBJUVZzIF7MOE0{KGmwZnXjeIVlKGmwZnXjeIVlKGmwIHj1cYFvKE2WMjDj[YxteyCjc4Pld5Nm\CCjczDy[YR2[3Srb36gbY4hUEmYMTDpcpRm\3KjdHXkJGRPSSCjdDCxJJVOKGGwZDDt[YF{fXKnZDDh[pRmeiB|MDDodpMheG:|dDDpcoZm[3Srb36gZpkhSWy3LVzUVkBRS1JicILveI9kd2xiYnHz[YQhdWW2aH;k NVPyPJBmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxM{C5PVY4QDBpPkOwPVk3PzhyPD;hQi=>
Assay
Methods Test Index PMID
Western blot CHOP / ATF-4 / XBP-1 / Lamin B 24625618
体内研究 Raltegravir 作用于携带 SIVmac251感染的非人类灵长类动物,提高病毒-免疫。Raltegravir单独给药非人类灵长类动物后,检测不到病毒载量。[5]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:

[1]

  • PFV 整合实验:

    为了定量分析链转移,供体DNA底物通过退火 HPLC 级寡核苷酸 5′-GACTCACTATAGGGCACGCGTCAAAATTCCATGACA 和 5′-ATTGTCATG GAATTTTGACGCGTGCCCTATAGTGAGTC而形成。反应(40 μL) 含0.75 μM PFV IN, 0.75 μM 供体 DNA, 4 nM (300 ng) 超螺旋 pGEM9-Zf(−) 靶 DNA, 125 mM NaCl, 5 mM MgSO4, 4 μM ZnCl2, 10 mM DTT, 0.8% (vol/vol) DMSO, 和 25 mM BisTris 丙烷–HCl, pH 7.45。加入指定浓度Raltegravir。加入2 μL PFV IN (在150 mM NaCl, 2 mM DTT, 和 10 mM Tris-HCl, pH 7.4中稀释)开始反应,在 37oC下反应1小时后,加入25 mM EDTA 和 0.5% (wt/vol) SDS终止反应。反应产物通过与 20 μg 蛋白酶 K 在 37oC下消化30分钟而脱蛋白,随后使用乙醇 沉淀,在 在1.5%琼脂糖凝胶上分离,然后通过用溴化乙锭染色观察。通过实时定量PCR, 使用 Platinum SYBR Green qPCR SuperMix 和三种引物 : 5′-CTACTTACTCTAGCTTCCCGGCAAC, 5′-TTCGCCAGTTAATAGTTTGCGCAAC, 和 5′-GACTCACTATAGGGCACGCGT定量分析整合产物。PCR 反应 (20 μL) 含0.5 μM 每种引物和1 μL 稀释的整合反应产物。在95oC下进行5分钟变性,在CFX96 PCR仪上进行35次循环,再在95oC下变性10秒,在56oC下退火30秒,在68oC下延伸1分钟。在INSTI存在时,使用连续稀释的WT PFV IN 反应,获得标准曲线。

细胞实验:

[5]

  • Cell lines: 人类MT-4 细胞
  • Concentrations: 0.0001 μM -1 μM
  • Incubation Time: 2小时
  • Method:

    使用 SIVmac251, HIV-1 (IIIB) 和 HIV-2 (CDC 77618)对人类MT-4细胞进行多重感染2小时。然后在PBS中冲洗细胞3次,在有或无一系列一式三份Raltegravir 浓度 (0.0001 μM -1 μM)时,按5 × 105/mL 悬浮在含新鲜培养基 (在原代细胞中加入 50 单位/mL IL-2 ) 的96孔板中。也制备未治疗的感染对照和模拟感染对照,用于比较不同处理法得到的实验数据。通过MTT法(MT-4/MTT实验 )定量分析致MT-4细胞死亡的病毒。显微镜检测发现病毒感染的细胞培养物由于缺乏成簇的能力而大量死亡。移液打断成簇,在 37oC下温育2小时后, 通过光学显微镜l (100 × 放大倍数)观察新簇形成。通过ELISA收集细胞培养上清液,用于测量HIV-1 p24 和 HIV-2/SIVmac251 p27核心抗原。在CEMx174感染的细胞培养物中,具有病毒包膜糖蛋白诱导形成多核体的倾向,按盲实验形式计数多核体,感染5天后,通过光学显微镜观察每孔。

动物实验:

[5]

  • Animal Models: 印度猕猴
  • Dosages: 50 mg/kg 或 100 mg/kg, 每天两次
  • Administration: 口服处理

溶解度(25°C)

体外

体内

从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+40% PEG 300+2% Tween 80+ddH2O

8mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 444.42
化学式

C20H21FN6O5

CAS号 518048-05-0
储存条件 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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

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,: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: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: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。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04513626 Recruiting Drug: DORAVIRINE 100 MG [Pifeltro] HIV Infections Centre de Recherches et d''Etude sur la Pathologie Tropicale et le Sida September 15 2020 Phase 2
NCT03667547 Completed Drug: Raltegravir Human Immunodeficiency Virus (HIV) Infection Merck Sharp & Dohme LLC September 27 2018 Phase 4
NCT03174977 Recruiting Drug: 18F-Raltegravir HIV-1-infection University of California San Francisco|Merck Sharp & Dohme LLC April 1 2018 Early Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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