NM107 (2'-C-Methylcytidine)
(Synonyms: 2'-C-甲基胞嘧啶核苷,2'-C-Methylcytidine; NM-107) 目录号 : GC33936
A ribonucleoside with broad-spectrum antiviral activity
Cas No.:20724-73-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
2'-C-Methylcytidine (2CMC) is a ribonucleoside with broad-spectrum antiviral activity.1 It reduces the number of viral plaques in BHK-21 cells infected with dengue type 2, reovirus type 1, West Nile, and yellow fever RNA viruses with EC50 values of 95, 26, 80, and 75 μM, respectively. 2CMC inhibits hepatitis C virus (HCV) replication (EC50 = 2.2 μM in a replicon assay) and protects MDBK cells from infection with bovine virus diarrhea virus (BVDV; EC50 = 2.2 μM) and human coronavirus (HCoV; EC50 = 90 μM). It also reduces infectious virus yield in BHK-21 cells infected with foot-and-mouth disease virus (FMDV; EC50 = 6.4 μM) and swine vesicular disease virus (SVDV; EC50 = 45.2 μM).2 In vivo, 2CMC reduces viral shedding to undetectable levels in a mouse model of persistent norovirus infection.3
1.Benzaria, S., Bardiot, D., Bouisset, T., et al.2′-C-Methyl branched pyrimidine ribonucleoside analogues: Potent inhibitors of RNA virus replicationAntivir. Chem. Chemother.18(4)225-242(2007) 2.Goris, N., De Palma, A., Toussaint, J.F., et al.2'-C-methylcytidine as a potent and selective inhibitor of the replication of foot-and-mouth disease virusAntiviral Res.73(3)161-168(2007) 3.Rocha-Pereira, J., Van Dycke, J., and Neyts, J.Treatment with a nucleoside polymerase inhibitor reduces shedding of murine norovirus in stool to undetectable levels without emergence of drug-resistant variantsAntimicrob. Agents Chemother.60(3)1907-1911(2015)
| Cas No. | 20724-73-6 | SDF | |
| 别名 | 2'-C-甲基胞嘧啶核苷,2'-C-Methylcytidine; NM-107 | ||
| Canonical SMILES | NC(C=CN1[C@@H]2O[C@H](CO)[C@@H](O)[C@@]2(C)O)=NC1=O | ||
| 分子式 | C10H15N3O5 | 分子量 | 257.24 |
| 溶解度 | Water : ≥ 50 mg/mL (194.37 mM) | 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 | 3.8874 mL | 19.4371 mL | 38.8742 mL |
| 5 mM | 0.7775 mL | 3.8874 mL | 7.7748 mL |
| 10 mM | 0.3887 mL | 1.9437 mL | 3.8874 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。
Phosphoramidate prodrugs of 2'-C-Methylcytidine for therapy of hepatitis C virus infection
J Med Chem 2009 Sep 10;52(17):5394-407.PMID:19725579DOI:10.1021/jm900447q.
The application of a phosphoramidate prodrug approach to 2'-C-Methylcytidine (NM107), the first nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, is reported. 2'-C-Methylcytidine, as its valyl ester prodrug (NM283), was efficacious in reducing the viral load in patients infected with HCV. Several of the phosphoramidates prepared demonstrated a 10- to 200-fold superior potency with respect to the parent nucleoside in the cell-based replicon assay. This is due to higher levels of 2'-C-Methylcytidine triphosphate in the cells. These prodrugs are efficiently activated and converted to the triphosphate in hepatocytes of several species. Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides.
Combinations of 2'-C-Methylcytidine analogues with interferon-alpha2b and triple combination with ribavirin in the hepatitis C virus replicon system
Antivir Chem Chemother 2008;19(1):25-31.PMID:18610555DOI:10.1177/095632020801900104.
Background: Hepatitis C virus (HCV) polymerase is an essential enzyme for HCV replication and has multiple inhibitor binding sites making it a major target for antiviral intervention. It is apparent that no single drug can inhibit HCV replication in humans. Hence, combinations of nucleoside analogues beta-D-2'-C-methylcytidine (2'-C-MeC; NM-107) or beta-D-2'-deoxy-2'-fluoro-2'-C-methyleytidine (2'-F-C-MeC; PSI-6130) with interferon-alpha2b (IFN-alpha2b) or triple combination with ribavirin (RBV) were evaluated. Methods: Huh-7 cells containing the self-replicating subgenomic HCV replicon (Clone B) were used for drug combination studies. After drug treatment for 5 days, total cellular RNA was then extracted and both ribosomal RNA and HCV replicon RNA were amplified in a single-step multiplex real-time PCR assay. Drug interaction analyses were performed using the CalcuSyn program. Results: Double combinations of 2'-C-MeC or 2'-F-C-MeC with IFN-alpha2b at all ratios tested had weighted average combination index (Cl(wt)) values <1 indicating synergistic inhibition of HCV replication in the replicon system. For the triple combinations of IFN-alpha2b plus RBV with either 2'-C-MeC or 2'-F-C-MeC, the Cl(wt) values at 1:1:1 ratio tested were 0.5 and 0.8, respectively, indicating synergistic antiviral effects. No apparent cytotoxicity effects were observed with any of the combinations tested. Conclusion: These promising in vitro data warrant clinical investigation of the nucleosides analogues such as 2'-C-MeC or 2'-F-C-MeC in their prodrug forms, together with IFN-alphac2b and RBV, for successful treatment of HCV infections.
Anti-hepatitis C virus activity of Acacia confusa extract via suppressing cyclooxygenase-2
Antiviral Res 2011 Jan;89(1):35-42.PMID:21075144DOI:10.1016/j.antiviral.2010.11.003.
Chronic hepatitis C virus (HCV) infection continues to be an important cause of morbidity and mortality by chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world. It is of tremendous importance to discover more effective and safer agents to improve the clinical treatment on HCV carriers. Here we report that the n-butanol-methanol extract obtained from Acacia confusa plant, referred as ACSB-M4, exhibited the inhibition of HCV RNA replication in the HCV replicon assay system, with an EC(50) value and CC(50)/EC(50) selective index (SI) of 5 ± 0.3 μg/ml and >100, respectively. Besides, ACSB-M4 showed antiviral synergy in combination with IFN-α and as HCV protease inhibitor (Telaprevir; VX-950) and polymerase inhibitor (2'-C-Methylcytidine; NM-107) by a multiple linear logistic model and isobologram analysis. A complementary approach involving the overexpression of COX-2 protein in ACSB-M4-treated HCV replicon cells was used to evaluate the antiviral action at the molecular level. ACSB-M4 significantly suppressed COX-2 expression in HCV replicon cells. Viral replication was gradually restored if COX-2 was added simultaneously with ACSB-M4, suggesting that the anti-HCV activity of ACSB-M4 was associated with down-regulation of COX-2, which was correlated with the suppression of nuclear factor-kappaB (NF-κB) activation. ACSB-M4 may serve as a potential protective agent for use in the management of patients with chronic HCV infection.
The hepatitis C virus replicon presents a higher barrier to resistance to nucleoside analogs than to nonnucleoside polymerase or protease inhibitors
Antimicrob Agents Chemother 2008 May;52(5):1604-12.PMID:18285474DOI:10.1128/AAC.01317-07.
Specific inhibitors of hepatitis C virus (HCV) replication that target the NS3/4A protease (e.g., VX-950) or the NS5B polymerase (e.g., R1479/R1626, PSI-6130/R7128, NM107/NM283, and HCV-796) have advanced into clinical development. Treatment of patients with VX-950 or HCV-796 rapidly selected for drug-resistant variants after a 14-day monotherapy treatment period. However, no viral resistance was identified after monotherapy with R1626 (prodrug of R1479) or NM283 (prodrug of NM107) after 14 days of monotherapy. Based upon the rapid selection of resistance to the protease and nonnucleoside inhibitors during clinical trials and the lack of selection of resistance to the nucleoside inhibitors, we used the replicon system to determine whether nucleoside inhibitors demonstrate a higher genetic barrier to resistance than protease and nonnucleoside inhibitors. Treatment of replicon cells with nucleoside inhibitors at 10 and 15 times the 50% effective concentration resulted in clearance of the replicon, while treatment with a nonnucleoside or protease inhibitor selected resistant colonies. In combination, the presence of a nucleoside inhibitor reduced the frequency of colonies resistant to the other classes of inhibitors. These results indicate that the HCV replicon presents a higher barrier to the selection of resistance to nucleoside inhibitors than to nonnucleoside or protease inhibitors. Furthermore, the combination of a nonnucleoside or protease inhibitor with a nucleoside polymerase inhibitor could have a clear clinical benefit through the delay of resistance emergence.
Green tea phenolic epicatechins inhibit hepatitis C virus replication via cycloxygenase-2 and attenuate virus-induced inflammation
PLoS One 2013;8(1):e54466.PMID:23365670DOI:10.1371/journal.pone.0054466.
Chronic hepatitis C virus (HCV) infection is the leading risk factor for hepatocellular carcinoma (HCC) and chronic liver disease worldwide. Green tea, in addition to being consumed as a healthy beverage, contains phenolic catechins that have been used as medicinal substances. In the present study, we illustrated that the epicatechin isomers (+)-epicatechin and (-)-epicatechin concentration-dependently inhibited HCV replication at nontoxic concentrations by using in vitro cell-based HCV replicon and JFH-1 infectious systems. In addition to significantly suppressing virus-induced cyclooxygenase-2 (COX-2) expression, our results revealed that the anti-HCV activity of the epicatechin isomers occurred through the down-regulation of COX-2. Furthermore, both the epicatechin isomers additively inhibited HCV replication in combination with either interferon-α or viral enzyme inhibitors [2'-C-Methylcytidine (NM-107) or telaprevir]. They also had prominent anti-inflammatory effects by inhibiting the gene expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and inducible nitrite oxide synthase as well as the COX-2 in viral protein-expressing hepatoma Huh-7 cells. Collectively, (+)-epicatechin and (-)-epicatechin may serve as therapeutic supplements for treating HCV-related diseases.