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Nolatrexed is a thymidylate synthase inhibitor (Ki = 11 nM).1 It inhibits cell growth in a panel of human and murine cancer cell lines (IC50s = 0.39-6.6 μM). Nolatrexed inhibits the growth of L1210 cells, an effect that is decreased by greater than 50-fold by the addition of exogenous thymidine. Nolatrexed (0.7 and 3.5 μM) induces cell cycle arrest at the S phase in L1210 cells. It increases life span in a thymidine kinase-deficient L5178Y/TK- murine lymphoma model when administered at doses ranging from 25 to 200 mg/kg.
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1. AG337, a novel lipophilic thymidylate synthase inhibitor: In vitro and in vivo preclinical studies. Cancer Chemother. Pharmacol. 37(6), 509-517 (1996).