7-Hydroxymethotrexate (7-OH-MTX) is the major and, frequently the only, pteridine metabolite found in bone-marrow aspirates of patients chronically treated with low-dose oral methotrexate (MTX) [Sonneveld, Schultz, Nooter and Hahlen (1986) Cancer Chemother. Pharmacol. 18, 111-116]. The Ki values for MTX and 7-OH-MTX for avian liver 5-amino-imidazole-4-carboxamide ribonucleotide transformylase differ by 4.5-fold in favour of 7-OH-MTX as the better inhibitor, while Ki values for avian liver glycinamide ribonucleotide transformylase differ by 1.9-fold favouring MTX as the better inhibitor. Thus 7-OH-MTX possesses a different enzyme-inhibiting repertoire from its parent drug and this information may be useful in explaining the mechanism of action of low-dose MTX therapies used to treat autoimmune disease.
Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis
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J E Baggott, S L Morgan, W H Vaughn; Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis. Biochem J 15 June 1994; 300 (3): 627–629. doi: https://doi.org/10.1042/bj3000627
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