PSI-6206

PSI-6206 (as known as RO-2433 or GS-331007), β-_D-2’-deoxy-2’-fluoro-2’-C-methyluridine, is the deaminated derivative of PSI-6130, β-_D-2’-deoxy-2’-fluoro-2’-C-methylcytidine, which is a potent inhibitor of hepatitis C virus (HCV) replication in the subgenomic HCV reolicon system.  PSI-6206, itself, does not shown any inhibitory activity towards HCV replication in the HCV subgenomic replicon system. However, the its triphosphate form, RO2433-TP, is a potent inhibitor of RNA synthesis by HCV polymerase, which inhibits both the RNA sysnthesis activity of HCV replicase (IC₅₀ = 1.19 uM) and the RNA synthesis activity of the recombinant HCV Con1 NS58 on a heteropolymeric RNA template derived from the 3’-end of the negative strand of the HCV genome (IC₅₀ = 0.52 uM and K_i = 0.141 uM).

Reference

Han Ma, Wen-Rong Jiang, Nicole Robledo, Vincent Leveque, Samir Ali, Teresa Lara-Jamie, Mohammad Masjedizadeh, David B. Smith, Nick Cammack, Klaus Klumpp, and Julian Symons. Characterization of the metabolic ctivation of hepatitis C virus nucleoside inhibitor β-_D-2’-deoxy-2’-fluoro-2’-C-methylcytidine (PSI-6130) and identification of a novel active 5’-triphosphate species. The Journal of Biological Chemistry 2007; 282(41): 29812-29820