| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
NiRAN[1]
AT-9010 tetrasodium targets the NiRAN (nidovirus RdRp-associated nucleotidyltransferase) domain, a crucial enzymatic function required for viral replication. As a nucleotide analog, it also inhibits viral polymerases by acting as a chain terminator during RNA synthesis. The compound is the active triphosphate metabolite of the prodrug AT-527. By inhibiting NiRAN and viral polymerase, it effectively suppresses the replication of SARS-CoV-2. Its mechanism involves incorporation into the growing RNA chain, leading to premature termination of viral RNA synthesis. |
|---|---|
| ln Vitro |
Normal human bronchial and nasal epithelial cells treated with 10 μM AT-511 (698 μM and 236 μM, respectively) produce significant levels of the active triphosphate metabolite AT-9010, which has a half-life of at least 38 hours [1].
In vitro studies have shown that AT-9010 tetrasodium is a potent inhibitor of viral replication. Normal human bronchial and nasal epithelial cells treated with AT-511 (the parent prodrug) produce significant levels of the active triphosphate metabolite AT-9010, with an intracellular half-life of at least 38 hours. The compound effectively inhibits the replication of SARS-CoV-2 in cell-based assays. Its activity is mediated through the inhibition of the NiRAN domain and viral polymerase, blocking the viral life cycle at the RNA synthesis stage. AT-9010 is used as a reference compound in antiviral screening assays. |
| ln Vivo |
In vivo, AT-9010 tetrasodium is the bioactive metabolite generated from the oral prodrug AT-527. AT-527 has been evaluated in clinical trials for the treatment of COVID-19, where the active triphosphate AT-9010 is formed intracellularly. The compound's antiviral efficacy in vivo is dependent on the conversion of the prodrug to the active triphosphate and its subsequent inhibition of viral replication. Studies in animal models have demonstrated that AT-527 administration leads to the production of AT-9010 and reduces viral loads. The compound's long intracellular half-life supports sustained antiviral activity.
|
| Enzyme Assay |
The in vitro enzyme assay for AT-9010 tetrasodium involves measuring the inhibition of the NiRAN domain or viral RNA polymerase activity. Purified NiRAN enzyme or viral polymerase is incubated with a RNA template, nucleotides, and varying concentrations of AT-9010. The incorporation of nucleotides or the synthesis of RNA is measured using radiolabeled substrates or fluorescence-based detection methods. The inhibition of enzymatic activity is determined from dose-response curves. IC50 values are calculated to quantify the potency of the compound against the target enzyme.
|
| Cell Assay |
In vitro cellular assays for AT-9010 tetrasodium are conducted using virus-infected cell lines, such as Vero E6 or human airway epithelial cells. Cells are infected with SARS-CoV-2 and treated with varying concentrations of AT-9010 or its prodrug AT-527. Viral replication is assessed by measuring viral RNA levels using qRT-PCR or by plaque assay to determine the viral titer. The compound's antiviral activity is expressed as the EC50 (half-maximal effective concentration). Cytotoxicity is assessed using standard cell viability assays to ensure that the observed antiviral effects are not due to compound toxicity.
|
| Animal Protocol |
In vivo animal studies for AT-9010 are typically performed by administering the prodrug AT-527 to animal models of SARS-CoV-2 infection, such as transgenic mice expressing human ACE2 or hamsters. Animals are treated with AT-527 via oral gavage at various doses. Viral loads in lung tissues and other organs are measured by qRT-PCR. Histopathological analysis is performed to assess lung inflammation and damage. Pharmacodynamic markers, such as the levels of the active triphosphate AT-9010 in tissues, are measured to confirm target engagement. Standard study designs with appropriate control groups are employed.
|
| ADME/Pharmacokinetics |
AT-9010 tetrasodium is a nucleotide analog with a molecular weight of 627.13 g/mol and a molecular formula of C11H13FN5Na4O13P3. As the active triphosphate metabolite of AT-527, it is formed intracellularly after administration of the prodrug. The compound has a long intracellular half-life of at least 38 hours in human airway epithelial cells. Its pharmacokinetic properties are characterized by efficient conversion from the prodrug and sustained intracellular levels, supporting once-daily or twice-daily dosing. The compound is water-soluble and is typically formulated for in vitro studies in aqueous buffers.
|
| Toxicity/Toxicokinetics |
Toxicology data for AT-9010 tetrasodium are derived from studies of its prodrug AT-527. As a nucleotide analog, the compound's safety profile is similar to other drugs in this class. Preclinical toxicology studies have evaluated the effects of AT-527 on hematological parameters, liver function, and renal function. The compound has been shown to be generally well-tolerated at therapeutic doses. However, nucleotide analogs can have off-target effects on host polymerases, leading to potential mitochondrial toxicity or effects on bone marrow. Comprehensive toxicology studies have been conducted to support clinical development.
|
| References | |
| Additional Infomation |
AT-9010 tetrasodium is a triphosphate bioactive metabolite of the antiviral prodrug AT-527 and a potent inhibitor of the NiRAN domain essential for viral replication. It has demonstrated efficacy in inhibiting SARS-CoV-2 replication. The compound is a nucleotide analog that acts as a viral polymerase inhibitor. AT-527, the parent prodrug, has been investigated in clinical trials for the treatment of COVID-19. AT-9010 is a valuable research tool for antiviral drug discovery and the study of RNA virus replication mechanisms. It is for research use only and is not approved for therapeutic use.
|
| Molecular Formula |
C11H13FN5NA4O13P3
|
|---|---|
| Molecular Weight |
627.13
|
| Exact Mass |
626.929
|
| CAS # |
1621884-18-1
|
| Related CAS # |
AT-9010;1261253-79-5;AT-9010 triethylamine;2648089-95-4
|
| PubChem CID |
166638290
|
| Appearance |
White to off-white solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
16
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
37
|
| Complexity |
952
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C[C@]1([C@@H]([C@@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)O[C@H]1N1C=NC2C(N=C(N)NC1=2)=O)O)F.[Na+].[Na+].[Na+].[Na+]
|
| InChi Key |
YSFIWHKJCYGPPP-ZJECJYFYSA-J
|
| InChi Code |
InChI=1S/C11H17FN5O13P3.4Na/c1-11(12)6(18)4(2-27-32(23,24)30-33(25,26)29-31(20,21)22)28-9(11)17-3-14-5-7(17)15-10(13)16-8(5)19;;;;/h3-4,6,9,18H,2H2,1H3,(H,23,24)(H,25,26)(H2,20,21,22)(H3,13,15,16,19);;;;/q;4*+1/p-4/t4-,6-,9-,11-;;;;/m1..../s1
|
| Chemical Name |
tetrasodium;[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
|
| 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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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)
|
| Solubility (In Vitro) |
H2O : 100 mg/mL (159.46 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (159.46 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5946 mL | 7.9728 mL | 15.9457 mL | |
| 5 mM | 0.3189 mL | 1.5946 mL | 3.1891 mL | |
| 10 mM | 0.1595 mL | 0.7973 mL | 1.5946 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
