GSK5852

GSK5852 (GSK2485852) is an HCV NS5B polymerase inhibitor, with an IC₅₀ value of 50 nM. GSK5852 displays antiviral activity and inhibits HCV with EC₅₀s of 3.0 nM (genotype 1a, GT1a) and 1.7 nM (GT1b), respectively^[1][2][3]. IC50 & Target:Target: 50 nM (NS5B, HCV)^[1] In Vitro: Nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase (RdRp) is a component of HCV, for researching HCV infection-related diseases^[1].
GSK5852 (compound 87) inhibits aggregation by two mechanisms: 1) stabilizing β-flap in a closed inactive state to inhibit the initiation step of the RdRp RNA replication cycle; 2) disruption of RNA processing channels through direct spatial contact^[1].
GSK5852 is a non-nucleoside NS5B inhibitor and exhibits inhibitory effect on HCV mutant variants with EC₅₀s of 3.2 nM (GT1a C316Y), 1.9 nM (GT1b C316N), respectively^[1].
GSK5852 displays an excellent resistance profile and shows a <5-fold potency loss across the clinically important NS5B resistance mutations^[2].
GSK5852 shows no cross-resistance against known resistance mutations in NS5B^[2].
GSK5852 (compound 3) (0-10 μM) blocks the initiation step of NS5B polymerase cycle^[3].
GSK5852 (0.6, 10 μM; 0-75 h) shows slow binding kinetics with isolated GT1b 316N protein, and with a dissociation half-life of >40 hours^[3].
GSK5852 (0.6, 10 μM; 15 min) inhibits NS5B∆21 1b 316N with an IC₅₀ value of 130 nM^[3].