MK-5172
(Synonyms: 格拉瑞韦; MK-5172) 目录号 : GC18004
MK-5172是一种丙型肝炎病毒（HCV）NS3/4a蛋白酶选择性抑制剂，对多种基因型及耐药变异株均具有广谱活性，并能抑制SARS-CoV-2 3CL蛋白酶活性。
Cas No.:1350514-68-9
Sample solution is provided at 25 µL, 10mM.
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MK-5172 is a selective inhibitor of hepatitis C virus (HCV) NS3/4a protease, exhibiting broad-spectrum activity against multiple genotypes and drug-resistant variants, and capable of inhibiting SARS-CoV-2 3CL protease activity[1-2]. MK-5172 demonstrates favorable liver-targeting properties and sustained virological responses in studies, making MK-5172 applicable for research related to chronic hepatitis C and MK-5172 co-infection with HIV[3-4].
In vitro, pretreatment of Vero E6 cells or human-derived 293T-ACE2 cells with MK-5172 (0.55-20.5μM) for 2 hours, followed by infection with SARS-CoV-2 virus (MOI=0.025–2PFU/cell) for 48 hours, significantly inhibited viral replication[5]. Treatment of GT1a (H77) replicon cells with MK-5172 (0.4–35nM) for 72 hours, MK-5172 significantly suppressed HCV RNA replication (EC₉₀=0.9nM) and maintained inhibitory activity against NS5A-resistant variants[6].
In vivo, intraperitoneal injection of MK-5172 (10mg/kg/day) for 5 days (starting from day 5 after MC-38 colon adenocarcinoma cell transplantation) in PD-1-mCherry-SMASh homozygous knock-in (KI) mice significantly suppressed tumor growth[7]. Oral administration of MK-5172 (3mg/kg) once daily for 3 consecutive days in diabetic model C57BL/6 mice significantly restored glucose homeostasis[8].
References:
[1] Vallet-Pichard A, Pol S. Grazoprevir/elbasvir combination therapy for HCV infection. Therap Adv Gastroenterol. 2017 Jan;10(1):155-167.
[2] Al-Salama ZT, Deeks ED. Elbasvir/Grazoprevir: A Review in Chronic HCV Genotypes 1 and 4. Drugs. 2017 May;77(8):911-921.
[3] Karaoui LR, Mansour H, Chahine EB. Elbasvir-grazoprevir: A new direct-acting antiviral combination for hepatitis C. Am J Health Syst Pharm. 2017 Oct 1;74(19):1533-1540.
[4] Wang SJ, Huang CF, Yu ML. Elbasvir and grazoprevir for the treatment of hepatitis C. Expert Rev Anti Infect Ther. 2021 Sep;19(9):1071-1081.
[5] Bafna K, White K, Harish B, et al. Hepatitis C virus drugs that inhibit SARS-CoV-2 papain-like protease synergize with remdesivir to suppress viral replication in cell culture. Cell Rep. 2021 May 18;35(7):109133.
[6] Lahser FC, Bystol K, Curry S, et al. The Combination of Grazoprevir, a Hepatitis C Virus (HCV) NS3/4A Protease Inhibitor, and Elbasvir, an HCV NS5A Inhibitor, Demonstrates a High Genetic Barrier to Resistance in HCV Genotype 1a Replicons. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2954-64.
[7] Naruse C, Sugihara K, Miyazaki T, et al. A degron system targeting endogenous PD-1 inhibits the growth of tumor cells in mice. NAR Cancer. 2022 Jun 17;4(2):zcac019.
[8] Shao J, Li S, Qiu X, et al. Engineered poly(A)-surrogates for translational regulation and therapeutic biocomputation in mammalian cells. Cell Res. 2024 Jan;34(1):31-46.
MK-5172是一种丙型肝炎病毒（HCV）NS3/4a蛋白酶选择性抑制剂，对多种基因型及耐药变异株均具有广谱活性，并能抑制SARS-CoV-2 3CL蛋白酶活性[1-2]。MK-5172在研究中显示出良好的肝脏靶向性和持久的病毒学应答，可用于慢性丙型肝炎及其与HIV共感染的相关研究[3-4]。
在体外，MK-5172（1.25–50μM）预处理Vero E6细胞或人源293T-ACE2细胞2小时，随后以SARS-CoV-2病毒（MOI=0.025–2PFU/cell）感染48小时，MK-5172显著抑制病毒复制[5]。MK-5172（0.4–35nM）处理GT1a（H77）复制子细胞72小时，MK-5172显著抑制HCV RNA复制（EC₉₀=0.9nM），且对NS5A耐药变异株仍保持抑制活性[6]。
在体内，MK-5172（10mg/kg/day）腹腔注射处理PD-1-mCherry-SMASh纯合敲入（KI）小鼠5天（从MC-38结肠腺癌细胞移植后第5天开始），MK-5172显著抑制肿瘤生长[7]。MK-5172（3mg/kg）口服给药处理糖尿病模型C57BL/6小鼠，每日一次连续3天，MK-5172显著恢复血糖稳态[8]。
| Cell experiment [1]: | |
Cell lines | Vero E6 cells (African green monkey kidney epithelial cell line) and human 293T cells expressing ACE2 |
Preparation Method | Vero E6 and 293T-ACE2 cells were maintained in Dulbecco's minimal essential medium (DMEM) supplemented with 10% fetal bovine serum (FBS). Cells were treated with MK-5172 (0.55-20.5μM) for 48 hours. |
Reaction Conditions | 4.2µM (in Vero E6 cells); 0.55-20.5µM range (in 293T-ACE2 cells); 48h. |
Applications | MK-5172 significantly inhibited SARS-CoV-2 replication in both Vero E6 (IC₅₀=4.2µM) and human 293T-ACE2 cells. MK-5172 demonstrated synergistic antiviral activity with remdesivir, increasing the efficacy of the polymerase inhibitor by up to 10-fold. The drug specifically inhibited the viral papain-like protease (PLpro) enzyme activity. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Diabetic mice were generated by Streptozotocin (STZ) injection. Mice received daily oral administration of MK-5172 for 3 consecutive days. Blood glucose and insulin levels were measured, and intraperitoneal glucose tolerance tests (GTTs) were performed. |
Dosage form | 3mg/kg; Oral gavage; Once daily for 3 days |
Applications | MK-5172 administration effectively restored glucose homeostasis in diabetic mice, significantly reducing fasting blood glucose levels and improving glucose tolerance. The drug triggered insulin expression from a genetically encoded MK-5172-inducible translational switch, demonstrating therapeutic efficacy in a disease model requiring on-demand drug secretion. |
References: | |
| Cas No. | 1350514-68-9 | SDF | |
| 别名 | 格拉瑞韦; MK-5172 | ||
| Canonical SMILES | COC1=CC2=C(N=C(CCCCC[C@@H]3C[C@H]3OC(N[C@@H](C(C)(C)C)C(N4[C@H](C(N[C@@]5(C(NS(=O)(C6CC6)=O)=O)[C@H](C5)C=C)=O)C[C@@H]7C4)=O)=O)C(O7)=N2)C=C1 | ||
| 分子式 | C38H50N6O9S | 分子量 | 766.9 |
| 溶解度 | ≥ 38.35 mg/mL in DMSO, ≥ 24 mg/mL in EtOH with ultrasonic and warming | 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 | 1.304 mL | 6.5198 mL | 13.0395 mL |
| 5 mM | 260.8 μL | 1.304 mL | 2.6079 mL |
| 10 mM | 130.4 μL | 652 μL | 1.304 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。
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