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GS-443902 trisodium

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Category Hepatitis C Virus (HCV)
CAS 1355050-21-3
Description GS-443902 trisodium is a potent inhibitor of viral RNA-dependent RNA-polymerases (RdRp), with IC50s of 1.1 µM, 5 µM for RSV RdRp and HCV RdRp, respectively.
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Product Information

Synonyms GS-441524 triphosphate trisodium; Remdesivir metabolite trisodium
IUPAC Name tetrasodium;[[[(2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxyoxolan-2-yl]methoxy-oxidophosphoryl]oxy-oxidophosphoryl] phosphate
Molecular Weight 619.13
Molecular Formula C12H12N5Na4O13P3
Canonical SMILES C1=C2C(=NC=NN2C(=C1)C3(C(C(C(O3)COP(=O)([O-])OP(=O)([O-])OP(=O)([O-])[O-])O)O)C#N)N.[Na+].[Na+].[Na+].[Na+]
InChI InChI=1S/C12H16N5O13P3.4Na/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);;;;/q;4*+1/p-4/t7-,9-,10-,12+;;;;/m1..../s1
InChIKey GONGCFUOBMNVIT-ZTYDICHKSA-J
Purity 99%
Solubility In Vitro:
H2O : 33.33 mg/mL(55.82 mM;Need ultrasonic)
Appearance White to light yellow (Solid)
Storage -80°C, protect from light, stored under nitrogen
* The compound is unstable in solutions, freshly prepared is recommended.
In Vitro In a continuous 72 h incubation of 1 µM Remdesivir (GS-5734), the GS-443902 trisodium (GS-441524 triphosphate trisodium; Remdesivir metabolite trisodium) level is measured at 2, 24, 48 and 72 h, and reaches a Cmax of 300, 110, and 90 pmol/million cells in macrophages, HMVEC, and HeLa cells lines respectively. GS-443902 trisodium (compound 8a) is a triphosphates (TP) derivative. GS-443902 trisodium (NTP; 0.01, 0.1, 1, 10, 100 μM) inhibits RSV RdRp-catalysed RNA synthesis by incorporating into the nascent viral RNA transcript and causing its premature termination. GS-5734 selectively inhibits EBOV replication by targeting its RdRp and inhibiting viral RNA synthesis following efficient intracellular conversion to GS-443902 sodium.
In Vivo Remdesivir (GS-5734; 10 mg kg; i.v.) rapidly distributes into peripheral blood mononuclear cells (PBMCs), and efficient conversion to GS-443902 trisodium (Remdesivir metabolite trisodium; NTP) is apparent within 2 h of dose administration in rhesus monkeys. In PBMCs, GS-443902 trisodium represents the predominant metabolite and is persistent with a t1/2 of 14 h and levels required for >50% virus inhibition for 24 hours.
Target IC50: 1.1 µM (RSV RdRp) and 5 µM (HCV RdRp)

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