GS-443902 (trisodium)

1355050-21-3

597.15

H2O : 300 mg/mL (502.39 mM; Need ultrasonic)

Cell Cycle/DNA Damage; Anti-infection; Anti-infection; Anti-infection; Metabolic Enzyme/Protease

GS-443902 trisodium (GS-441524 triphosphate trisodium) is a potent viral RNA-dependent RNA-polymerases (RdRp) inhibitor with IC₅₀s of 1.1 uM, 5 uM for RSV RdRp and HCV RdRp, respectively. GS-443902 trisodium is the active triphosphate metabolite of Remdesivir (GS-5734)^[1][2]. IC50 & Target: IC50: 1.1 uM (RSV RdRp) and 5 uM (HCV RdRp)^[1][2] In Vitro: In a continuous 72 h incubation of 1 uM 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 C_max of 300, 110, and 90 pmol/million cells in macrophages, HMVEC, and HeLa cells lines respectively^[1].
GS-443902 trisodium (compound 8a) is a triphosphates (TP) derivative^[2].
GS-443902 trisodium (NTP; 0.01, 0.1, 1, 10, 100 uM) 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^[3].
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 t_1/2 of 14?h and levels required for >50% virus inhibition for 24?hours^[3].