PSI-6130

Short Summary : Inhibitor of HCV nucleoside polymerase,selective and effective

Category : Proteases|HCV Protease

Purity : 0.98

CAS Number : 817204-33-4

Formula : C10H14FN3O4

Molecular Weight : 259.23

SMILE : CC1(C(C(OC1N2C=CC(=NC2=O)N)CO)O)F

Solubility : Soluble in DMSO

Storage : Store at -20°C

Description : PSI-6130 is a selective and effective inhibitor of hepatitis C virus (HCV) RNA replication with an EC50 of 0.46 ?M. It is a potent nucleoside analog which incorporates into nascent RNA by the HCV NS5B polymerase and leads to chain termination. [1]NS5B is a viral protein discovered in hepatitis c virus. It plays a significant role in the replication of HCV, which uses HCV’S viral positive RNA strand as the template and catalyzes the polymerization of rNTP during RNA replication. PSI-6130 is a nucleotide analog and it can be activated by converting into nucleotide triphosphate form, which can be an alternative substrate in the synthesis of viral RNA. As a result PSI-6130 reduces the efficacy of further elongation of HCV RNA by NS5B. [2]Studies reported PSI-6130 HCV replication inhibition effects. PSI-6130 activity of HCV replication was determined in Huh7 cells with a subgenomic genotype 1b Con1 strain. And the mean IC50 was 0.6 ?M. And another study showed that PSI-6130 inhibited HCV GT-1b (Con1 strain) and GT-1a (H77 strain) subgenomic RNA replication, with similar levels of potency, whose mean EC 50 values are 0.51 and 0.30 ?M, respectively. [1, 2]PSI-6130 could be transformed into two active metabolites, RO2433 and PSI-6026 respectively, in human primary hepatocytes by enzymes. Moreover, PSI-6130 showed little or no cytotoxicity against different cells, including human peripheral blood mononuclear and human bone marrow progenitor cells. [1, 3]Assessments of PSI-6130’s activity against other viruses in the Flaviviridae family were conducted, which illustrated that PSI-6130 was not active against viruses including BVDV, WNV, YFV, HBV, and HIV. The results also showed that PSI-6130 is a selective HCV inhibitor. [3]References:1.Ali S, Leveque V, Le Pogam S, et al. Selected replicon variants with low-level in vitro resistance to the hepatitis C virus NS5B polymerase inhibitor PSI-6130 lack cross-resistance with R1479. Antimicrobial agents and chemotherapy[J], 2008, 52(12): 4356-4369.2.Ma H, Jiang W R, Robledo N, et al. Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor ?-d-2′-deoxy-2′-fluoro-2′-C-methylcytidine (PSI-6130) and identification of a novel active 5′-triphosphate species[J]. Journal of Biological Chemistry, 2007, 282(41): 29812-29820.3.Stuyver L J, McBrayer T R, Tharnish P M, et al. Inhibition of hepatitis C replicon RNA synthesis by beta-D-2′-deoxy-2′-fluoro-2′-C-methylcytidine: a specific inhibitor of hepatitis C virus replication[J]. Antiviral chemistry & chemotherapy, 2006, 17(2): 79-87.

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