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NM-107

Alias: NM-107; NM 107; NM107; 2'-C-Methylcytidine; 2'-C-MeC; 2-CMC; mCyd ; 2'CMeC; 2CMC.
Cat No.:V14696 Purity: ≥98%
NM-107 (2'-C-Methylcytidine; 2'CMeC; 2'-C-MeC; mCyd; 2CMC) is a novel, potent and selective anti-viral agent acting as an inhibitor of the hepatitis C virus (HCV) NS5B polymerase.
NM-107
NM-107 Chemical Structure CAS No.: 20724-73-6
Product category: HCV
This product is for research use only, not for human use. We do not sell to patients.
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50mg
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Product Description
NM-107 (2'-C-Methylcytidine; 2'CMeC; 2'-C-MeC; mCyd; 2CMC) is a novel, potent and selective anti-viral agent acting as an inhibitor of the hepatitis C virus (HCV) NS5B polymerase.
NM-107 (2'-C-Methylcytidine) is a ribonucleoside analog with broad-spectrum antiviral activity, functioning as a nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase.
Biological Activity I Assay Protocols (From Reference)
Targets
HCV
NM-107 targets the HCV NS5B RNA-dependent RNA polymerase, acting as a nucleoside inhibitor that terminates viral RNA chain elongation.
ln Vitro
In Huh7-1 cells and cell culture-propagated HCV, NM107 (25 μM; 24 hours) treatment reduces intracellular RNA levels and extracellular viral titers.
In vitro, NM-107 inhibits HCV replication with an EC50 of 1.85 μM in wild-type replicon cells. It also inhibits bovine viral diarrhea virus (BVDV) replication with an EC50 of 2.2 μM and human coronavirus (HCoV) with an EC50 of 90 μM. It demonstrates an IC50 of 7.0 μM against HCV RNA replication in vitro.
ln Vivo
In vivo, NM-107 has shown antiviral activity in animal models as a nucleoside inhibitor. Its active triphosphate form is the primary inhibitor of viral polymerase, leading to a reduction in viral load. It has been investigated as a potential therapeutic agent for HCV infection.
Enzyme Assay
In vitro enzyme assays for NM-107 involve measuring the inhibition of the HCV NS5B polymerase. The enzyme is incubated with a RNA template, primer, and nucleotide substrates, including the compound's triphosphate form (NM-107-TP), which is the active species. The incorporation of the nucleotide analog into the growing RNA chain leads to chain termination, which is measured to determine the inhibitory potency.
Cell Assay
Cell Line: Huh7-1 cells and HCV (HCVcc) propagated in cell culture Concentration: 25 μM Incubation Time: 24 hours Result: The reduction of intracellular RNA levels coincided with the titers of extracellular viruses.
In vitro cellular assays for NM-107 use HCV subgenomic replicon cell lines. Cells are treated with the compound, and viral RNA replication is quantified by real-time RT-PCR. The compound is typically tested in a panel of cell lines, including those harboring wild-type and drug-resistant replicons, to determine its EC50 and selectivity index. Cytotoxicity is assessed in parallel to ensure the antiviral effect is not due to general cell death.
Animal Protocol
In vivo animal studies for NM-107 are conducted using mouse models of HCV infection, such as transgenic mice expressing the HCV replicon or chimeric mice with humanized livers. The compound is administered orally or intraperitoneally, and viral load in the serum or liver is measured to assess efficacy. Other models using bovine viral diarrhea virus (BVDV) in calves have also been used.
ADME/Pharmacokinetics
As a nucleoside analog, NM-107 is a prodrug that requires intracellular phosphorylation to its active triphosphate form. PK studies focus on the formation and persistence of the active triphosphate in target cells (hepatocytes). The compound has been evaluated in preclinical models for its oral bioavailability and liver distribution.
Toxicity/Toxicokinetics
Toxicological data for NM-107 are not detailed in publicly available sources. As a nucleoside analog, potential toxicity concerns include mitochondrial toxicity and effects on host DNA polymerases. Standard preclinical safety assessments would be required for its development as an antiviral agent.
References

[1]. Combinations of cyclophilin inhibitor NIM811 with hepatitis C Virus NS3-4A Protease or NS5B polymerase inhibitors enhance antiviral activity and suppress the emergence of resistance. Antimicrob Agents Chemother. 2008 Sep;52(9):3267-75.

[2]. Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Proc Natl Acad Sci U S A. 2013 Mar 5;110(10):3991-6.

[3]. Characterization of the activity of 2'-C-methylcytidine against dengue virus replication. Antiviral Res. 2015 Apr;116:1-9.

Additional Infomation
A nucleoside analogue with anti-hepatitis C virus (HCV) activity. Phosphorylation of this metabolite to its 5-triphosphate form inhibits viral RNA chain elongation and the activity of viral RNA-dependent RNA polymerase. This blocks the production of HCV RNA, thereby inhibiting viral replication.
NM-107 is the parent nucleoside of the clinically approved prodrug NM-283 (Valopicitabine). It is a 2'-C-methylcytidine. It has broad-spectrum antiviral activity against flavi- and pestiviruses. Its development as a direct antiviral for HCV was largely superseded by more effective direct-acting antivirals.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C10H15N3O5
Molecular Weight
257.2432
Exact Mass
257.101
Elemental Analysis
C, 46.69; H, 5.88; N, 16.33; O, 31.10
CAS #
20724-73-6
PubChem CID
500902
Appearance
White to off-white solid powder
Density
1.7±0.1 g/cm3
Boiling Point
523.9±60.0 °C at 760 mmHg
Melting Point
243-245ºC
Flash Point
270.7±32.9 °C
Vapour Pressure
0.0±3.1 mmHg at 25°C
Index of Refraction
1.700
LogP
-0.8
Hydrogen Bond Donor Count
4
Hydrogen Bond Acceptor Count
5
Rotatable Bond Count
2
Heavy Atom Count
18
Complexity
424
Defined Atom Stereocenter Count
4
SMILES
O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@](C([H])([H])[H])([C@]1([H])N1C(N=C(C([H])=C1[H])N([H])[H])=O)O[H])O[H]
InChi Key
PPUDLEUZKVJXSZ-VPCXQMTMSA-N
InChi Code
InChI=1S/C10H15N3O5/c1-10(17)7(15)5(4-14)18-8(10)13-3-2-6(11)12-9(13)16/h2-3,5,7-8,14-15,17H,4H2,1H3,(H2,11,12,16)/t5-,7-,8-,10-/m1/s1
Chemical Name
4-amino-1-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidin-2(1H)-one
Synonyms
NM-107; NM 107; NM107; 2'-C-Methylcytidine; 2'-C-MeC; 2-CMC; mCyd ; 2'CMeC; 2CMC.
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO : 100 mg/mL (388.74 mM)
H2O : ≥ 50 mg/mL (194.37 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.5 mg/mL (9.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (9.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.


Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (9.72 mM)

Solubility in Formulation 5: 50 mg/mL (194.37 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

Calculator

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

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An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
  • Enter 350.26 in the Molecular Weight (MW) box
  • Enter 10 in the Concentration box and choose the correct unit (mM)
  • Enter 5 in the Volume box and choose the correct unit (mL)
  • Click the “Calculate” button
  • The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
  • Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
  • Enter 25 into the Concentration (End) box and select the correct unit (mM)
  • Enter 25 into the Volume (End) box and choose the correct unit (mL)
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  • The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box
g/mol

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:
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Definitions of molecular mass, molecular weight, molar mass and molar weight:
  • Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
  • Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Biological Data
  • Chemical structures of various HCV inhibitors and their activities in the 48-h replicon assay as single treatment.[1].Antimicrob Agents Chemother. 2008 Sep;52(9):3267-75.
  • Combination of NIM811 with various HCV protease or polymerase inhibitors in the 48-h HCV replicon assay.[1].Antimicrob Agents Chemother. 2008 Sep;52(9):3267-75.
  • Synergy analysis for the combination of NIM811 with HCV protease or polymerase inhibitors.[1].Antimicrob Agents Chemother. 2008 Sep;52(9):3267-75.
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