Raltitrexed

Raltitrexed is an inhibitor of thymidylate synthase and an antimetabolite drug used for cancer treatment. In Vitro: Raltitrexed inhibits HepG2 proliferation by arresting the cell cycle at G0/G1, and the cell cycle is mediated via downregulation of cyclin A and CDK2^[1]. Raltitrexed (0.1, 0.5, 2.5 μg/mL) decreases the viability of SGC7901 cells in a dose- and time-dependent manner. Raltitrexed (0.5 μg/mL) shows typical apoptotic morphology, including nuclear shrinkage, fragmentation, chromatin condensation and apoptotic bodies in SGC7901 cells. Raltitrexed blocks the cell cycle at the G0/G1 phase, decreases in the mitochondrial membrane potential. Raltitrexed also increases the level of ROS, induces caspase-3-dependent apoptosis via activation of the mitochondria, and increases TS protein and mRNA expression levels^[3]. Raltitrexed (1.5 nM) reduces the number of GM00637 cells, selectively induces gene conversions, but does not affect DSB-induced HR or NHEJ^[4]. In Vivo: Raltitrexed (0, 5, 10, 11.5, 13.5, 15 mg/kg b/w, i.p.) increases the rates of resorbed embryos and growth retardation of murine model of NTDs in a dose dependent manner. Raltitrexed (11.5 mg/kg b/w) maximally inhibits the thymidylate synthase (TS) activity in embryonic tissue, decreases dTMP levels and while increases dUMP levels^[2].