Bristol-Myers Squibb (BMS) is developing entecavir, a viral replication inhibitor, for the potential treatment of hepatitis B virus (HBV) infection [220240]. The compound is a cyclopentyl guanosine analog and is in phase II trials in the US [383065]. Entecavir was originally developed as SQ-34676 for the treatment of herpes simplex virus infections [221992], but displayed only moderate activity which eventually led to discontinuation of development for this indication. However, Bristol-Myers Squibb later discovered that entecavir was extremely potent against HBV (ED50 = 3.0 nM, compared with 200 nM for lamivudine) with relatively low toxicity (CC50 = 30,000 nM) [221986] and acted through inhibition of DNA polymerase [220240]. The triphosphate form is a potent HBV polymerase inhibitor in both woodchuck and duck models [306056]. By September 2000, a large-scale clinical trial was underway in China for HBV infection [400209] and by October 2000 phase I trials were ongoing in Japan [384751]. In March 2001 SG Cowen predicted sales of US$25 million in 2002, US$50 million in 2003 and US$75 million in 2004 [403751].