LY2334737 is an orally available prodrug of gemcitabine with antineoplastic activity.

Five cell lines expressing CES2 responded to LY2334737 treatment, which was less cytotoxic to SK-OV-3 CES2 knockdown than to parental cells. CES2-transfected HCT-116 cell drug response correlated with CES2 expression level. Bystander studies showed significantly greater PC-3-GFP growth inhibition by LY2334737 when cocultured with CES2, not mock transfectants [1].

Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once daily for 21 days showed significantly greater tumor growth inhibition in CES2 transfectants compared to mock transfectants (P ≤ 0.001) [1]. The MTD was 40 mg LY2334737. Fatigue was the most frequent DLT for LY2334737 monotherapy (4 patients), followed by elevated transaminase levels (2 patients), both observed at the 40-50 mg dose levels. In the combination arm, 2 of 10 patients experienced DLTs at the 40 mg dose level, which included fatigue and elevated liver enzyme levels [2]. Metronomic LY2334737 administration increased blood flow in luciferase-tagged LM2-4 tumor xenografts, measurable via contrast micro-ultrasound, and coincided with a relative increase in tumor bioluminescence [3].