Valnivudine (FV-100 free base), a prodrug of CF-1743, is an orally active anti-herpes zoster (HZ) nucleoside analogue. CF-1743, a bicyclic nucleoside analog (BCNA), has highly specific antiviral activity against varicella-zoster virus (VZV). Valnivudine is rapidly and extensively converted to CF-1743 in vivo[1][2].
In vitro cytotoxicity studies in normal human primary hepatocytes, keratinocytes, and rapidly dividing HepG2 cells, Valnivudine (FV-100 free base) demonstrates mean 50% cytotoxic concentration values of >10 μM[2]. CF-1743 (compound 4f) has anti-varicella-zoster virus (VZV) activity in VZV OKA (EC50=0.3 nM), VZV YS (EC50=0.1 nM) in HEL cell[3].
[1]. Nathan B Price, et al. Progress in the development of new therapies for herpesvirus infections. Curr Opin Virol. 2011 Dec;1(6):548-54. [2]. Helen S Pentikis, et al. Pharmacokinetics and safety of FV-100, a novel oral anti-herpes zoster nucleoside analogue, administered in single and multiple doses to healthy young adult and elderly adult volunteers. Antimicrob Agents Chemother. 2011 Jun;55(6):2847-54. [3]. C McGuigan, et al. Highly potent and selective inhibition of varicella-zoster virus by bicyclic furopyrimidine nucleosides bearing an aryl side chain. J Med Chem. 2000 Dec 28;43(26):4993-7.