| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
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| Targets |
Viral RNA-dependent RNA polymerase (RdRp) of coronaviruses (e.g., SARS-CoV-2, MERS-CoV) and filoviruses (e.g., Ebola virus), acting as the direct antiviral metabolite after intracellular phosphorylation [1]
Mediated by the viral polymerase complex, with susceptibility influenced by viral proofreading exoribonuclease (ExoN) activity [2]
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| ln Vitro |
• Antiviral activity: The triphosphorylated metabolite of Remdesivir nucleoside monophosphate (GS-443902) inhibited Ebola virus (EBOV) replication in HeLa cells with EC₅₀ = 0.11 μM [1].
• Mechanism of action: The active triphosphate metabolite (GS-443902) acts as a nucleotide analog, competing with ATP for incorporation into viral RNA by RdRp, causing delayed chain termination 3–5 nucleotides downstream of incorporation [1]. • Coronavirus susceptibility: In SARS-CoV-2, the antiviral activity of Remdesivir (which delivers the monophosphate) is reduced by ExoN proofreading activity. ExoN-deficient SARS-CoV-2 mutants showed 6-fold lower EC₅₀ values (greater susceptibility) compared to wild-type virus in Vero E6 cells [2] |
| Enzyme Assay |
• Antiviral activity: The triphosphorylated metabolite of Remdesivir nucleoside monophosphate (GS-443902) inhibited Ebola virus (EBOV) replication in HeLa cells with EC₅₀ = 0.11 μM [1].
• Mechanism of action: The active triphosphate metabolite (GS-443902) acts as a nucleotide analog, competing with ATP for incorporation into viral RNA by RdRp, causing delayed chain termination 3–5 nucleotides downstream of incorporation [1]. • Coronavirus susceptibility: In SARS-CoV-2, the antiviral activity of Remdesivir (which delivers the monophosphate) is reduced by ExoN proofreading activity. ExoN-deficient SARS-CoV-2 mutants showed 6-fold lower EC₅₀ values (greater susceptibility) compared to wild-type virus in Vero E6 cells [2] |
| Cell Assay |
• Viral replication inhibition: Vero E6 cells infected with SARS-CoV-2 (wild-type or ExoN-mutant) at MOI 0.01. Treated with Remdesivir (source of the monophosphate metabolite) for 48 hours. Viral RNA quantified by qRT-PCR; EC₅₀ calculated from dose-response curves. ExoN-deficient virus EC₅₀ = 0.009 μM vs wild-type EC₅₀ = 0.054 μM [2].
• Metabolite detection: Huh7 cells treated with Remdesivir (10 μM). Intracellular metabolites (including nucleoside monophosphate and triphosphate forms) extracted and quantified via LC-MS/MS at 24 hours, confirming efficient phosphorylation [1] |
| ADME/Pharmacokinetics |
• Metabolic activation: Remdesivir is hydrolyzed intracellularly to the nucleoside monophosphate (GS-441524 monophosphate) by cathepsin A/carboxylesterase 1, then phosphorylated to the active triphosphate (GS-443902) by cellular kinases [1].
• Intracellular half-life: The triphosphate metabolite (GS-443902) has a prolonged intracellular half-life (>14 hours) in primary human macrophages, supporting sustained antiviral activity [1] |
| References |
[1]. US20160122374.
[2]. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. MBio. 2018 Mar 6;9(2). pii: e00221-18. |
| Additional Infomation |
• Remdesivir nucleoside monophosphate is an obligate intracellular intermediate metabolite of the prodrug Remdesivir (GS-5734), essential for forming the active triphosphate inhibitor of viral RdRp [1].
• Viral ExoN proofreading activity (e.g., in SARS-CoV-2) can limit efficacy by excising the incorporated monophosphate analog from viral RNA, requiring higher drug concentrations for inhibition [2] GS-441524 monophosphate is a C-nucleoside phosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a phosphate group. In cells, GS-441524 monophosphate gets converted into the pharmacologically active triphosphate form (GS-443902). It has a role as an anticoronaviral agent, an antiviral drug and a drug metabolite. It is a C-nucleoside phosphate, an aromatic amine, a nitrile and a pyrrolotriazine. It is functionally related to a GS-441524. |
| Molecular Formula |
C12H14N5O7P
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|---|---|
| Molecular Weight |
371.2426
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| Exact Mass |
371.063
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| CAS # |
1911578-74-9
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| PubChem CID |
121310009
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| Appearance |
White to off-white solid powder
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| LogP |
-3.1
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
25
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| Complexity |
610
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C1=C2C(=NC=NN2C(=C1)[C@]3([C@@H]([C@@H]([C@H](O3)COP(=O)(O)O)O)O)C#N)N
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| InChi Key |
ZBHOHJWLOOFLMW-LTGWCKQJSA-N
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| InChi Code |
InChI=1S/C12H14N5O7P/c13-4-12(8-2-1-6-11(14)15-5-16-17(6)8)10(19)9(18)7(24-12)3-23-25(20,21)22/h1-2,5,7,9-10,18-19H,3H2,(H2,14,15,16)(H2,20,21,22)/t7-,9-,10-,12+/m1/s1
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| Chemical Name |
[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : 25 mg/mL (67.34 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6937 mL | 13.4684 mL | 26.9368 mL | |
| 5 mM | 0.5387 mL | 2.6937 mL | 5.3874 mL | |
| 10 mM | 0.2694 mL | 1.3468 mL | 2.6937 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.
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.
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