LY2334737 is an nucleoside analog and is an orally active proagent of Gemcitabine. LY2334737 exhibits inhibitory activity against enterovirus A71 (EV-A71) infection. LY2334737 has antiviral and anticancer effects[1][2].
ly2334737 is an oral prodrug of gemcitabine, the clinically efficacious anticancer agent [1].ly2334737 has been shown the hydrolytic activity by carboxylesterase 2 (ces2). the michaelis-menten kinetic parameters are exhibited to be : km of 43μm and vmax of 40nmol/min/mg protein. in addition, ly2334737 has been found to be cytotoxic to cells in the ncl-60 panel with the ec50 values of 0.512±0.016μm, 0.402±0.018μm and 0.034±0.002μm for pc-gfp alone, hct-116 mock transfectant and hct-116 ces2 transfectant cell lines, respectively. apart from these, the study result has been noted that parental sk-ov-3 cells were approximately 4-fold more sensitive to ly2334737 cytotoxicity than the sk-ov-3 knockdown with the ec50 values of 1.1μm and 4.5μm, respectively [1].
Oral treatment of xenograft models with 3.2 mg/kg LY2334737 once a day for 21 days shows greater tumor growth inhibition of CES2 transfectant than the mock transfectant[1].
Metronomic LY2334737 administration causes increased blood flow in luciferase-tagged LM2-4 tumor xenografts, and this effect, readily measured using contrast micro-ultrasound, coincided with a relative increase in tumor bioluminescence[3].
[1] pratt se1, durland-busbice s, shepard rl, heinz-taheny k, iversen pw, dantzig ah. human carboxylesterase-2 hydrolyzes the prodrug of gemcitabine (ly2334737) and confers prodrug sensitivity to cancer cells. clin cancer res. 2013 mar 1;19(5):1159-68.
