| Size | Price | |
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| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
GS-646089 (compound 2) can inhibit RSV replication in primary NHBE cells and HEp-2 cells, with EC50 values of 6.23 μM and 6.83 μM, respectively; in addition, it has no cytotoxicity to HEp-2 cells and MT4 cells at concentrations up to 50 μM[1]. The active triphosphate metabolite (2-NTP) of GS-646089 can effectively inhibit RSV RNP complex, with an IC50 value of 0.050 μM, and has high selectivity for human mitochondrial polymerase and DNA polymerase[1]. GS-646089 can effectively inhibit the enzymatic activity of cell-free RSV-A2 RNP complex and RdRp, with IC50 values of 46 nM and 43 nM, respectively[2]. GS-646089 inhibited RSV replication in NHBE cells with an EC50 of approximately 2–7 μM and showed no cytotoxicity at concentrations up to 50 μM [3]. GS-646089 also inhibited RSV replication in HEp-2 cells with an EC50 of approximately 2–7 μM; it showed no cytotoxicity in HEp-2 or MT4 cells even at the highest concentration of 50 μM [3]. The low levels of intracellular active 2-NTP metabolites produced by GS-646089 (10 μM; 2 h) suggest that the initial phosphorylation of this nucleoside is limited [3].
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| ln Vivo |
GS-646089 (compound 2) (1.6-7.6 mg/kg; inhalation; once daily; 6 days) is the active metabolite of inhaled GS-7682, which can reduce the RSV viral load in the bronchoalveolar lavage fluid (BALF) of African green monkeys infected with respiratory syncytial virus (RSV) by an average of 3.6 log10 and significantly inhibit the replication of the virus in the lower respiratory tract [1]. GS-646089 (1.6-7.6 mg/kg; nebulized inhalation; once daily; 6 days) can reduce the RSV A2 viral load in the BALF of African green monkeys by an average of 3.6 log10 on day 5 post-infection, and the viral load continues to decrease until day 11 compared with the solvent control group [3].
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| Animal Protocol |
Animal/Disease Models:African Green Monkeys (infected with RSV A2 on day 0) [1]
Doses: 1.6 mg/kg; 7.6 mg/kg Route of Administration: Once daily for 6 days Experimental Results: High levels of active GS-646089 metabolites (2-NTPs) were detected in lung tissue. Compared with the vector control group, the viral load in bronchoalveolar lavage fluid (BAL) was reduced by an average of 3.6 log10 on day 5. RSV RNA copy number was significantly reduced in BAL samples collected from day 3 to 11 post-infection. Moderate viral rebound occurred 2 to 4 days after the last dose, but the viral load in the treated African Green Monkeys remained low on day 11. No statistically significant reduction in viral load was observed in nasal swabs. Animal/Disease Models:African green monkey [3] Doses: 1.6 mg/kg; 7.6 mg/kg Route of Administration: Intratracheal nebulization; once daily for 6 days Experimental Results: Compared with the vector control group, the viral load in bronchoalveolar lavage fluid (BAL) decreased by an average of 3.6 log10 on day 5 post-infection. Respiratory syncytial virus (RSV) RNA copy number was significantly reduced in BAL samples collected from day 3 to 11 post-infection. A moderate rebound in BAL viral load occurred 2–4 days after the last administration, but the viral load remained lower than that in the vector control group until day 11. No statistically significant reduction in viral load was observed in nasal swab samples. |
| References |
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| Molecular Formula |
C12H13N5O4
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|---|---|
| Molecular Weight |
291.26
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| CAS # |
1770840-57-7
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
NC1=NC=NN2C1=CC=C2[C@H]3[C@H](O)[C@H](O)[C@](CO)(C#N)O3
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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) |
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
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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 | 3.4334 mL | 17.1668 mL | 34.3336 mL | |
| 5 mM | 0.6867 mL | 3.4334 mL | 6.8667 mL | |
| 10 mM | 0.3433 mL | 1.7167 mL | 3.4334 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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