| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
HCV(EC50: 5-28 nM);SARS-CoV-2(EC90: 0.47 μM)
Bemnifosbuvir targets the hepatitis C virus (HCV) RNA-dependent RNA polymerase (NS5B) and also inhibits the replication of SARS-CoV-2. It acts as a nucleotide prodrug that, upon cellular uptake and conversion to its active triphosphate form, interferes with viral RNA synthesis. The compound demonstrates pan-genotypic antiviral activities against multiple HCV genotypes. |
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| ln Vitro |
Pan-genotypic antiviral activities of bemnifosbuvir hemisulfate inhibit the replication of HCV genotype 1a (HCV GT1a), HCV genotype 1b, HCV GT2a, HCV GT3a, HCV GT4a, and HCV GT5a, with EC50 values of 12.8 nM, 12.5 nM, 9.2 nM, 10.3 nM, 14.7 nM, and 28.5 nM, respectively[1].
The concentration of Bemnifosbuvir hemisulfate needed to prevent SARS-CoV-2 replication by EC90 in normal human airway epithelial cells is 0.47 μM, which is comparable to the concentration of EC90 needed to prevent HCoV-229E, HCoV-OC43, and SARS-CoV in Huh-7 cells[2]. In vitro, bemnifosbuvir inhibits the replication of HCV genotypes 1a, 1b, 2a, 3a, 4a, and 5a with EC50 values of 12.8 nM, 12.5 nM, 9.2 nM, 10.3 nM, 14.7 nM, and 28.5 nM, respectively. It prevents SARS-CoV-2 replication in normal human airway epithelial cells with an EC90 of 0.47 µM. The compound also shows activity against HCoV-229E (EC90=2.8 µM), HCoV-OC43 (EC90=1.2 µM), and SARS-CoV (EC90=37 µM). |
| ln Vivo |
High levels of AT-9010 are preferentially delivered in the liver in vivo by bemnifosbuvir hemisulfate when given orally to rats (500 mg/kg) and monkeys (30 mg/kg, 100 mg/kg, or 300 mg/kg)[1].
In vivo, oral administration of bemnifosbuvir hemisulfate to rats (500 mg/kg) and monkeys (30, 100, or 300 mg/kg) results in high levels of AT-9010 preferentially delivered to the liver. This liver-targeting property is beneficial for treating HCV infections. The compound is being developed as an oral antiviral agent. |
| Enzyme Assay |
The in vitro enzyme assay typically measures the inhibition of HCV NS5B polymerase or the viral RNA-dependent RNA polymerase activity. The compound, as a prodrug, is first converted to its active triphosphate form in cells, which then competes with natural nucleotides for incorporation into the growing viral RNA chain, causing chain termination. Standard polymerase inhibition assays with purified enzyme and radiolabeled substrates are used to determine the IC50/EC50 values.
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| Cell Assay |
Cellular assays are performed using HCV replicon cell lines (e.g., Huh-7 cells) or SARS-CoV-2-infected human airway epithelial cells. Cells are treated with varying concentrations of the compound for a defined period, after which viral RNA levels are quantified by RT-qPCR or reporter gene assays. EC50 and EC90 values are calculated from dose-response curves to assess antiviral potency.
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| Animal Protocol |
In vivo animal studies involve oral administration of bemnifosbuvir to rats and cynomolgus monkeys at specified doses. Blood and tissue samples (particularly liver) are collected at various time points to measure the concentration of the active metabolite AT-9010. Efficacy studies are conducted in appropriate animal models of viral infection, though specific efficacy data for HCV or SARS-CoV-2 in animals are not detailed in the provided sources.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of bemnifosbuvir are characterized by its role as an oral prodrug that delivers the active metabolite AT-9010 preferentially to the liver. In rats (500 mg/kg) and monkeys (30-300 mg/kg), oral administration results in high hepatic concentrations of AT-9010. The compound has good oral bioavailability and is designed to achieve therapeutic concentrations in target tissues.
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| Toxicity/Toxicokinetics |
Specific toxicity data for bemnifosbuvir hemisulfate are not detailed in the provided search results. As a nucleoside analog prodrug, it may share class-related toxicities such as mitochondrial or hematologic effects, but these have not been specified. The compound is intended for oral administration and has been evaluated in clinical trials for safety, though specific toxicological profiles are not available from the current sources.
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| References |
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| Additional Infomation |
Bemnifosbuvir sulfate is the sulfate form of Bemnifosbuvir, a highly bioavailable, direct-acting antiviral purine nucleotide prodrug with potential antiviral activity against various RNA viruses. After oral administration, Bemnifosbuvir, as a prodrug, is metabolized into its active form. This active form inhibits the activity of viral RNA-dependent RNA polymerase, thereby terminating viral RNA transcription, reducing viral RNA production, and inhibiting viral RNA replication.
Mechanism of Action AT-527 is a guanylic acid analog prodrug with the potential to effectively inhibit SARS-CoV-2 replication in vitro. It also inhibits NS5B polymerase in hepatitis C virus. Currently, this drug is being studied for COVID-19, and has previously been studied for hepatitis C virus infection. Bemnifosbuvir is being developed for the treatment of HCV and COVID-19. It is an orally bioavailable direct-acting antiviral and purine nucleotide prodrug. The compound is currently in clinical development, though specific trial phases and outcomes are not detailed in the provided information. It is intended for research use only and not for human therapeutic use. |
| Molecular Formula |
C24H33FN7O7P
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|---|---|
| Molecular Weight |
581.533689260483
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| Exact Mass |
1260.4
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| CAS # |
2241337-84-6
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| Related CAS # |
Bemnifosbuvir;1998705-64-8;HCV-IN-31;1998705-62-6
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| PubChem CID |
155926085
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
10
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| Hydrogen Bond Acceptor Count |
32
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
85
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| Complexity |
1000
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| Defined Atom Stereocenter Count |
12
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| SMILES |
C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=NC3=C(N=C(N=C32)N)NC)(C)F)O)OC4=CC=CC=C4.C[C@@H](C(=O)OC(C)C)N[P@](=O)(OC[C@@H]1[C@H]([C@@]([C@@H](O1)N2C=NC3=C(N=C(N=C32)N)NC)(C)F)O)OC4=CC=CC=C4.OS(=O)(=O)O
|
| InChi Key |
QIGYBLSWYRTXCA-NVSCJZCKSA-N
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| InChi Code |
InChI=1S/2C24H33FN7O7P.H2O4S/c2*1-13(2)37-21(34)14(3)31-40(35,39-15-9-7-6-8-10-15)36-11-16-18(33)24(4,25)22(38-16)32-12-28-17-19(27-5)29-23(26)30-20(17)32;1-5(2,3)4/h2*6-10,12-14,16,18,22,33H,11H2,1-5H3,(H,31,35)(H3,26,27,29,30);(H2,1,2,3,4)/t2*14-,16+,18+,22+,24+,40-;/m00./s1
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| Chemical Name |
propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-[2-amino-6-(methylamino)purin-9-yl]-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate;sulfuric acid
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| Synonyms |
AT 527; AT-527; AT527; RG 6422; RG-6422; RG6422; Bemnifosbuvir hemisulfate; AT-511 hemisulfate; AT511; AT-511
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~180 mg/mL (~285.45 mM)
H2O : ≥ 100 mg/mL (~158.58 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (7.93 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 50.0 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: ≥ 5 mg/mL (7.93 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (7.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7196 mL | 8.5980 mL | 17.1960 mL | |
| 5 mM | 0.3439 mL | 1.7196 mL | 3.4392 mL | |
| 10 mM | 0.1720 mL | 0.8598 mL | 1.7196 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.
A Phase 2 Study Assessing the Safety and Efficacy of AT-527 in Combination with Daclatasvir in Subjects with Chronic HCV Infection
CTID: null
Phase: Phase 2 Status: Completed
Date: 2019-05-20
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