| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Viral RNA-dependent RNA polymerase (RdRp) of coronaviruses (e.g., SARS-CoV-2, MERS-CoV) and other RNA viruses [1]
Inhibitor of SARS-CoV-2 replication [2] |
|---|---|
| ln Vitro |
• SARS-CoV-2 inhibition: Inhibited SARS-CoV-2 replication in Vero E6 cells with EC₅₀ = 0.77 μM (24 hpi) and 0.23 μM (48 hpi) [2].
• Mechanism dependency: Activity against SARS-CoV-2 is reduced by viral proofreading exoribonuclease (ExoN). ExoN-deficient mutants showed 6-fold lower EC₅₀ (0.054 μM) vs wild-type (0.31 μM) in Calu-3 cells [1]. • Broad-spectrum activity: Effectively inhibited clinical isolate of SARS-CoV-2 (2019-nCoV BetaCoV/Wuhan/WIV04/2019) in Vero E6 cells (EC₅₀ = 0.65 μM at 48 h) [2]. • Cytotoxicity: CC₅₀ > 100 μM in Vero E6 and Huh-7 cells, indicating high selectivity index [2] |
| ln Vivo |
The administration of 3 mg/kg GS-5734 results in improved survival regardless of the time at which the treatment is started. Following three days of viral exposure, all animals receiving 10 mg/kg GS-5734 treatments reach the end of their in-life phase. Animals given repeated doses of 10 mg/kg GS-5734, however, consistently exhibit stronger antiviral effects. Clinical disease signs and markers of coagulopathy and end organ pathophysiology related to EVD are associated with improvement when treated with the 10 mg/kg D3 regimen (starting 3 days after virus exposure).
|
| Enzyme Assay |
• RdRp inhibition: Recombinant SARS-CoV-2 RdRp complex (nsp12/7/8) incubated with RNA template, NTPs, and varying concentrations of the active triphosphate metabolite (GS-443902). RNA synthesis quantified by radiolabeled UTP incorporation. GS-443902 competitively inhibited natural nucleotide incorporation with IC₅₀ = 3.65 μM [1].
• Chain termination assay: Primer extension reactions with RdRp showed GS-443902 incorporation caused RNA chain termination 3–5 nucleotides downstream [1] |
| Cell Assay |
• Viral replication kinetics: Vero E6 or Calu-3 cells infected with SARS-CoV-2 (MOI = 0.01–0.1). Treated with Remdesivir (0.1–10 μM) for 24–72 h. Viral RNA quantified by qRT-PCR; viral titers measured by plaque assay [1][2].
• Metabolite analysis: Huh-7 cells treated with 10 μM Remdesivir. Intracellular metabolites (mono-/tri-phosphate) extracted at 24 h and quantified via LC-MS/MS [1] |
| Animal Protocol |
• Mouse PK study: CD-1 mice received IV Remdesivir (10 mg/kg in 30% PEG-400/20% HP-β-CD). Plasma and tissues collected at 0.08–24 h. Lung concentrations measured [3].
• Rhesus monkey PK: Animals dosed IV with 10 mg/kg Remdesivir (30% PEG-400/20% HP-β-CD). Plasma and lung samples analyzed at multiple time points [3] |
| ADME/Pharmacokinetics |
• Lung exposure optimization: Prodrug modifications increased lung-to-plasma ratio by 3-fold in mice. Lung Cₘₐₓ = 3,200 ng/g vs plasma Cₘₐₓ = 1,100 ng/mL after IV 10 mg/kg [3].
• Metabolic stability: Remdesivir is rapidly hydrolyzed to nucleoside monophosphate (GS-441524) by cathepsin A/carboxylesterase 1, then phosphorylated to active triphosphate (GS-443902) [1]. • Species comparison: Lung AUC₀–₂₄ in monkeys (1,500 ng•h/g) was 2.5× higher than in mice (600 ng•h/g) at equivalent IV doses [3] |
| Toxicity/Toxicokinetics |
• Lung exposure optimization: Prodrug modifications increased lung-to-plasma ratio by 3-fold in mice. Lung Cₘₐₓ = 3,200 ng/g vs plasma Cₘₐₓ = 1,100 ng/mL after IV 10 mg/kg [3].
• Metabolic stability: Remdesivir is rapidly hydrolyzed to nucleoside monophosphate (GS-441524) by cathepsin A/carboxylesterase 1, then phosphorylated to active triphosphate (GS-443902) [1]. • Species comparison: Lung AUC₀–₂₄ in monkeys (1,500 ng•h/g) was 2.5× higher than in mice (600 ng•h/g) at equivalent IV doses [3] |
| References |
|
| Additional Infomation |
• Prodrug optimization improved lung targeting: New analogs achieved lung Cₘₐₓ 3,200 ng/g vs parent compound 1,100 ng/g in mice [3].
• ExoN proofreading activity reduces susceptibility; ExoN-deficient coronaviruses are hypersensitive [1]. • Proposed mechanism: Delayed RNA chain termination after incorporation of active triphosphate metabolite [1] |
| Molecular Formula |
C31H39N6O12P
|
|---|---|
| Molecular Weight |
718.65
|
| Elemental Analysis |
C, 51.81; H, 5.47; N, 11.69; O, 26.71; P, 4.31
|
| CAS # |
2250110-53-1
|
| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
CCC(CC)COC(=O)[C@H](C)NP(=O)(OC[C@@H]1[C@H]([C@H]([C@](O1)(C#N)C2=CC=C3N2N=CN=C3N)O)O)OC4=CC=CC=C4.C(=C\C(=O)O)\C(=O)O
|
| Synonyms |
GS-5734 maleate; GS 5734 Maleic acid salt; orb1739749; 2250110-53-1
|
| 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 (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.3915 mL | 6.9575 mL | 13.9150 mL | |
| 5 mM | 0.2783 mL | 1.3915 mL | 2.7830 mL | |
| 10 mM | 0.1391 mL | 0.6957 mL | 1.3915 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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