| Size | Price | Stock | Qty |
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| 1mg |
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| Other Sizes |
| Targets |
The molecular target of GS-441524-d is the same as the unlabeled parent compound. GS-441524 is a nucleoside analog that targets the viral RNA-dependent RNA polymerase (RdRp) of coronaviruses (including SARS-CoV-2 and feline coronavirus, FIPV). It is a competitive inhibitor. Once inside the cell, GS-441524 is phosphorylated to its triphosphate form (GS-441524-TP). The triphosphate mimics ATP and is incorporated into the growing viral RNA chain, causing chain termination and inhibiting viral replication. The deuterated version has the same mechanism as the unlabeled drug but is used for analytical purposes.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Studies involving the human use of drugs labeled with deuterium suggest that these compounds may offer some advantages when compared with their nondeuterated counterparts. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs. Deutetrabenazine is the first deuterated drug to receive Food and Drug Administration approval. This deuterated form of the drug tetrabenazine is indicated for the treatment of chorea associated with Huntington's disease as well as tardive dyskinesia. Ongoing clinical trials suggest that a number of other deuterated compounds are being evaluated for the treatment of human diseases and not merely as research tools.
GS-441524-d is not used in biological activity assays. The unlabeled GS-441524 exhibits potent antiviral activity. It shows strong inhibitory effects on feline infectious peritonitis virus (FIPV), with an EC₅0 value of 0.78 microM. It also shows similar activity in primary human lung and cat cell models infected with SARS-CoV-2. GS-441524 demonstrates superior activity compared to remdesivir itself in some in vitro models. It is an orally bioavailable and CNS-penetrant nucleoside analog. |
| ln Vivo |
Deuterated compounds may, in some cases, offer advantages over nondeuterated forms, often through alterations in clearance. Deuteration may also redirect metabolic pathways in directions that reduce toxicities. The approval of additional deuterated compounds may soon follow. Clinicians will need to be familiar with the dosing, efficacy, potential side effects, and unique metabolic profiles of these new entities.
GS-441524-d is not administered in vivo. The unlabeled GS-441524 is a potent antiviral agent in vivo. It has been used for the treatment of feline infectious peritonitis (FIP) in cats, a usually fatal disease caused by a coronavirus. In human COVID-19 patients, GS-441524 is a metabolite of remdesivir. GS-441524-d is an analytical standard used to quantify GS-441524 in pharmacokinetic studies of remdesivir and GS-441524. The compound is not a drug itself; it is a research tool. |
| Enzyme Assay |
A standard analytical protocol for the quantification of GS-441524 in plasma uses liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples (50 uL) are spiked with 10 uL of GS-441524-d internal standard (100 ng/mL). The sample is extracted by protein precipitation with acetonitrile. The supernatant is injected onto a C18 reverse-phase column (2.1 × 50 mm, 1.7 um). The mobile phase is water/acetonitrile with 0.1% formic acid. Detection is performed in positive ion mode using multiple reaction monitoring (MRM) transition m/z 292 → 160 (for GS-441524) and m/z 293 → 160 (for the d-labeled internal standard). The calibration range is 1-1000 ng/mL.
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| Cell Assay |
GS-441524-d is not used in cell-based assays. For antiviral activity assays, Vero E6 cells are seeded in 96-well plates and infected with SARS-CoV-2 (MOI 0.01). After 1 h, the virus is removed, and the cells are treated with varying concentrations of unlabeled GS-441524 (0.01-100 uM). After 48 h, cell viability is measured by MTT assay. For FIPV, cat cells (e.g., Felis catus whole fetus-4 cells) are used. The EC₅0 is calculated. The labeled standard is not used in these studies.
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| Animal Protocol |
For pharmacokinetic studies of GS-441524, male Sprague-Dawley rats (200-250 g, n=6/group) are administered GS-441524 (2-20 mg/kg) orally (PO) or intravenously (IV). Blood samples are collected at 0, 0.5, 1, 2, 4, 6, 8, 12, 24 h post-dose. GS-441524-d is added to each plasma sample as an internal standard before extraction. The concentration of unlabeled GS-441524 in plasma is quantified by LC-MS/MS. PK parameters (Cmax, Tmax, AUC, t½, bioavailability) are calculated by non-compartmental analysis using Phoenix WinNonlin software.
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| ADME/Pharmacokinetics |
GS-441524-d is an analytical standard, not a drug. GS-441524, the unlabeled parent compound, has a molecular weight of 291.26 Da, LogP 0.14, and is water-soluble. Following oral administration, the bioavailability is approximately 50-80% in animals. The half-life in rats is 4-6 hours. The compound is not significantly metabolized; the primary route of elimination is renal excretion. For research use, GS-441524-d is stored as a solid at -20degC, protected from light and moisture. The isotopic purity is >99%.
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| Toxicity/Toxicokinetics |
For GS-441524-d, hazard statements: H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation). Signal word: Warning. Precautionary statements: P261 (Avoid breathing dust/fume/gas/mist/vapors/spray), P280 (Wear protective gloves/protective clothing/eye protection/face protection), P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes). Storage: at -20degC, sealed, protected from light. For research use only (RUO).
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| References |
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| Additional Infomation |
GS-441524-d (CAS# 2647440-98-8) is a research-grade stable isotope-labeled internal standard. It is not an FDA-approved drug. It is used as an internal standard for the quantification of GS-441524 (the active metabolite of remdesivir) in biological samples by LC-MS/MS for pharmacokinetic (PK) and bioequivalence (BE) studies. For research use only, not for diagnostic or therapeutic applications.
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| Molecular Formula |
C12H12DN5O4
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|---|---|
| Molecular Weight |
292.27
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| Exact Mass |
292.103
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| CAS # |
2647440-98-8
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| Related CAS # |
GS-441524; GS-441524 hydrochloride
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| PubChem CID |
176523136
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| Appearance |
Typically exists as solids at room temperature
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| Hydrogen Bond Donor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
531
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| Defined Atom Stereocenter Count |
4
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| SMILES |
[2H]C1=C2C(=N)N=CNN2C(=C1)[C@]3([C@@H]([C@@H]([C@H](O3)CO)O)O)C#N
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| InChi Key |
BRDWIEOJOWJCLU-FLHNBJMXSA-N
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| InChi Code |
InChI=1S/C12H13N5O4/c13-4-12(10(20)9(19)7(3-18)21-12)8-2-1-6-11(14)15-5-16-17(6)8/h1-2,5,7,9-10,18-20H,3H2,(H2,14,15,16)/t7-,9-,10-,12+/m1/s1/i1D
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| Chemical Name |
(2R,3R,4S,5R)-2-(5-deuterio-4-imino-1H-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(hydroxymethyl)oxolane-2-carbonitrile
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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 | 3.4215 mL | 17.1075 mL | 34.2149 mL | |
| 5 mM | 0.6843 mL | 3.4215 mL | 6.8430 mL | |
| 10 mM | 0.3421 mL | 1.7107 mL | 3.4215 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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