TYMS and neoplasm: We did not proceed with testing PLX in in vivo mouse models, since earlier experiments by us and others clearly demonstrated that endogenous high folate levels in mouse blood and tissues (including tumor models) (Schmitz et al., 1994) protected these mice not only against systemic toxicity of methotrexate and antifolate based thymidylate synthase inhibitors but also reduced (or completely prevented) antitumor effect (Worzalla et al., 1998; Cao et al., 1999; Van der Wilt et al., 2001; Mauritz et al., 2008).