LY2334737 an orally active amide prodrug of gemcitabine, a nucleoside analog chemotherapeutic with a broad spectrum of anti-tumor activity against several human malignancies including pancreatic, ovarian, lung, breast, and bladder. LY2334737 was developed to be absorbed intact and cleaved in vivo, releasing gemcitabine and valproic acid to achieve prolonged systemic exposure, good efficacy with lower toxicity along with added flexibility of administration and greater patient convenience. The hydrolysis and pharmacokinetics of LY2334737 and its downstream metabolites was evaluated in preclinical in vitro and in vivo experiments in mice, rats, and dogs, which demonstrated the prodrug is absorbed largely intact across the intestinal epithelium and delivers LY2334737 to systemic circulation. The hydrolysis of LY2334737 is relatively slow, resulting in sustained release of gemcitabine in vivo. A major enzyme involved in the hydrolysis of LY2334737 is carboxylesterase 2 (CES2). The compound has entered clinical trials and is being evaluated as a potential new anticancer agent.