| Size | Price | |
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| 2mg | ||
| 5mg | ||
| 10mg | ||
| 25mg |
GS443902 (GS-441524 triphosphate), the triphosphate metabolite (active) of Remdesivir (GS-5734; Veklury) which is an FDA approved drug for treating COVID-19, is a novel highly potent viral RNA-dependent RNA-polymerases (RdRp) inhibitor with IC50s of 1.1 µM, 5 µM for RSV RdRp and HCV RdRp, respectively. It is the active triphosphate metabolite of Remdesivir.
| Targets |
RdRp (RNA-dependent RNA-polymerases)
|
|---|---|
| ln Vitro |
After being continuously incubated with 1 µM remdesivir (GS-5734) for 72 hours, the levels of GS-443902 (GS-441524 triphosphate; remdesivir metabolite; compound 4tp) were determined at 2, 24, 48, and 72 hours. , and in macrophages, HMVEC, and HeLa cell lines, respectively, obtained Cmax values of 300, 110, and 90 pmol/million cells [1]. Compound 8a, GS-443902, is a derivative of triphosphate (TP) [2]. GS-443902 (NTP; 0.01, 0.1, 1, 10, 100 μM) integrates into immature viral RNA transcripts and causes their premature termination, hence inhibiting RSV RdRp-catalyzed RNA production. After being effectively converted to GS-443902 in cells, GS-5734 specifically inhibits EBOV replication by targeting its RdRp and suppressing viral RNA synthesis [3].
|
| ln Vivo |
Remdesivir (GS-5734; 10 mg kg; intravenous injection) enters peripheral blood mononuclear cells (PBMC) quickly, and after two hours of administration, it is significantly and efficiently transformed to GS-443902 (GS-441524 III). NTP; phosphate; metabolite of remdesivir. Rhesus monkey. With a t1/2 length of 14 hours and levels necessary for >50% viral suppression at 24 hours, GS-443902 is the primary metabolite in PBMC [3].
|
| References |
[1]. Siegel D, et al. Discovery and Synthesis of a Phosphoramidate Prodrug of a Pyrrolo[2,1-f][triazin-4-amino] Adenine C-Nucleoside (GS-5734) for the Treatment of Ebola and Emerging Viruses. Med Chem. 2017 Mar 9;60(5):1648-1661.
[2]. Cho A, et al. Synthesis and antiviral activity of a series of 1'-substituted 4-aza-7,9-dideazaadenosine C-nucleosides. Bioorg Med Chem Lett. 2012 Apr 15;22(8):2705-7. [3]. Warren TK, et al. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys. Nature. 2016 Mar 17;531(7594):381-5. |
| Additional Infomation |
GS-443902 is an organic triphosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a triphosphate group. It is the active metabolite of remdesivir. It has a role as a drug metabolite, an antiviral drug and an anticoronaviral agent. It is a C-nucleoside, an aromatic amine, a nitrile, a pyrrolotriazine and an organic triphosphate. It is functionally related to a GS-441524.
|
| Molecular Formula |
C₁₂H₁₆N₅O₁₃P₃
|
|---|---|
| Molecular Weight |
531.202425003052
|
| Exact Mass |
530.9957
|
| CAS # |
1355149-45-9
|
| Related CAS # |
GS-441524;1191237-69-0;Remdesivir;1809249-37-3;GS-443902 trisodium;1355050-21-3
|
| PubChem CID |
56832906
|
| Appearance |
Typically exists as White to light yellow solids at room temperature
|
| Density |
2.4±0.1 g/cm3
|
| Index of Refraction |
1.841
|
| LogP |
-5.92
|
| SMILES |
NC1=NC=NN2C([C@]3(C#N)O[C@@H]([C@H]([C@H]3O)O)COP(O)(OP(O)(OP(O)(O)=O)=O)=O)=CC=C12
|
| InChi Key |
DFVPCNAMNAPBCX-LTGWCKQJSA-N
|
| InChi Code |
InChI=1S/C12H16N5O13P3/c13-4-12(8-2-1-6-11(14)15-5-16-17(6)8)10(19)9(18)7(28-12)3-27-32(23,24)30-33(25,26)29-31(20,21)22/h1-2,5,7,9-10,18-19H,3H2,(H,23,24)(H,25,26)(H2,14,15,16)(H2,20,21,22)/t7-,9-,10-,12+/m1/s1
|
| Chemical Name |
((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxytetrahydrofuran-2-yl)methyl
tetrahydrogen triphosphate
|
| Synonyms |
Remdesivir triphosphate metabolite; GS-441524 triphosphate;
GS 441524 triphosphate; GS441524 triphosphate; GS443902; GS-443902; GS-441524 Triphosphate; RDV-TP; AEL0YED4SU; UNII-AEL0YED4SU; [[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate; GS443902
|
| 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). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (2). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| 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 (~188.25 mM)
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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 | 1.8825 mL | 9.4127 mL | 18.8253 mL | |
| 5 mM | 0.3765 mL | 1.8825 mL | 3.7651 mL | |
| 10 mM | 0.1883 mL | 0.9413 mL | 1.8825 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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