GS-646089
GS-646089 is a broad-spectrum antiviral nucleoside analog that exhibits significant inhibitory activity against respiratory syncytial virus (RSV), human metapneumovirus (hMPV), rhinovirus (enterovirus) and enteroviruses. The IC50 of GS-646089 targeting RNA-dependent RNA polymerase (RdRp) ranges from 43 to 46 nM. GS-646089 blocks viral replication by being converted into a triphosphate metabolite intracellularly, which competes with ATP for incorporation into nascent RNA strands and acts as an immediate chain terminator. GS-646089 is the parent compound of the double prodrug GS-7682 (HY-161877), and is used in studies of acute respiratory viral infections and infections caused by related pathogens.
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- CAS 番号: 1770840-57-7
- 分子式: C12H13N5O4
- 分子量:291.26
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
DNA/RNA Synthesis アイソフォーム固有の製品をすべて表示
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生物活性
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RNA Polymerase |
RNASE L |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEp-2 | CC50 |
50 μM
Compound: 1
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Cytotoxicity against human Hep2 cells
Cytotoxicity against human Hep2 cells
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[PMID: 26191357] |
GS-646089 (compound 2) inhibits RSV replication in primary NHBE cells and HEp-2 cells, with EC50 values of 6.23 μM and 6.83 μM, respectively; additionally, it shows no cytotoxicity against HEp-2 cells and MT4 cells at concentrations up to 50 μM[1].
The active triphosphate metabolite (2-NTP) of GS-646089 potently inhibits the RSV RNP complex with an IC50 of 0.050 μM, and exhibits high selectivity for human mitochondrial polymerase and DNA polymerase[1].
GS-646089 potently inhibits cell-free RSV-A2 RNP complex and RdRp enzymatic activity, with IC50 values of 46 nM and 43 nM, respectively[2].
GS-646089 inhibits RSV replication in NHBE cells with an EC50 of approximately 2-7 μM, and shows no cytotoxicity at concentrations up to 50 μM[3].
GS-646089 inhibits RSV replication in HEp-2 cells with an EC50 of approximately 2-7 μM; it shows no cytotoxicity to HEp-2 or MT4 cells even at the highest concentration of 50 μM[3].
GS-646089 (10 μM; 2 h) generates low levels of intracellular active 2-NTP metabolites, indicating that the initial phosphorylation of this nucleoside is limited[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Spinal Cord Concentration | Cmax | AUC0-24 |
|---|---|---|---|---|---|---|
| Monkey[1] | 5 mg/kg | i.v. | 8.71 ± 3.01 h | / | 0.961 ± 0.379 μM | 6.03 ± 3.75 μM·h |
| Monkey[1] | 4.0 mg/kg | i.t. | 38.8 ± 4.0 h | / | 0.14 ± 0.05 μM | 2.55 ± 0.61 μM·h |
| Monkey[1] | 5.9 mg/kg | i.t. | 14.7 ± 2.6 h | / | 0.22 ± 0.09 μM | 3.39 ± 1.11 μM·h |
| Cynomolgus Monkey[2] | 5 mg/kg | i.v. | 8.71 ± 3.01 h | / | / | / |
| Cynomolgus Monkey[3] | 5 mg/kg | i.v. | 8.71 ± 3.01 h | 4.28 ± 1.32 | / | / |
GS-646089 (1.6-7.6 mg/kg; intratracheal nebulized aerosol; once daily; 6 days) achieves an average 3.6 log10 reduction in RSV A2 viral load in African Green Monkey BAL fluid by day 5 post-infection, with sustained lower viral loads relative to vehicle controls through day 11[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:AGM (infected with RSV A2 on day 0)[1]
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Dosage:1.6 mg/kg; 7.6 mg/kg
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Administration:i.t.; once daily; 6 days
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Result:Detected high levels of active GS-646089 metabolite (2-NTP) in lung tissue.
Achieved an average 3.6 log10 reduction in BAL viral load compared to vehicle control on day 5.
Resulted in significant reductions in RSV RNA copies in BAL fluid samples collected between 3 and 11 days post-infection.
Showed moderate viral rebound 2 to 4 days after final dose, but viral loads remained lower in treated AGMs through day 11.
Failed to produce statistically significant reductions in nasal swab viral loads.
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Animal Model:Chlorocebus aethiops[3]
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Dosage:1.6 mg/kg; 7.6 mg/kg
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Administration:intratracheal nebulized aerosol; once daily; 6 days
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Result:Achieved an average 3.6 log10 reduction in BAL viral load compared to vehicle controls on day 5 post-infection.
Showed significant reductions in RSV RNA copies in BAL samples collected between 3 and 11 days post-infection.
Exhibited moderate rebound in BAL viral loads 2-4 days after final dose, but viral loads remained lower than vehicle controls until day 11.
Did not achieve statistically significant viral load reductions in nasal swabs.
化学情報
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CAS 番号 1770840-57-7
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分子量 291.26
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分子式 C12H13N5O4
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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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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[2]. Suresh RR, et al. Prodrug strategies in developing antiviral nucleoside analogs. RSC Med Chem. 2026;17(1):105-131. Published 2026 Jan 2. [Content Brief]
[3]. Siegel DS, et al. Discovery of GS-7682, a Novel 4'-Cyano-Modified C-Nucleoside Prodrug with Broad Activity against Pneumo- and Picornaviruses and Efficacy in RSV-Infected African Green Monkeys. J Med Chem. 2024;67(15):12945-12968. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
GS-646089 関連分類
HY-185215 関連分類
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