Gemcitabine elaidate is a lipophilic prodrug form of the nucleoside analog gemcitabine that contains an elaidic acid moiety.1 Gemcitabine elaidate inhibits growth of gemcitabine-sensitive L1210/L5, BCLO, and A2780 cells (IC50s = 0.0033, 0.0042, and 0.0025 ?M, respectively) but not cytarabine-resistant L4A6 and Bara-C cells (IC50s = 16 and 13 ?M, respectively) or gemcitabine-resistant AG6000 cells (IC50 = 91 ?M). It inhibits growth of THX, LOX, MOLT-4, and MOLT-4/C8 cells in a manner independent of nucleoside transport. Gemcitabine elaidate reduces tumor growth in EKVX non-small cell lung cancer and MHMX sarcoma mouse xenograft models but not in an H-146 small cell lung cancer mouse xenograft model when administered at a dose of 40 mg/kg every three days.
1.Bergman, A.M., Adema, A.D., Balzarini, J., et al.Antiproliferative activity, mechanism of action and oral antitumor activity of CP-4126, a fatty acid derivative of gemcitabine, in in vitro and in vivo tumor modelsInvest. New Drugs29(3)456-466(2011)