Differences in methotrexate and 7-hydroxymethotrexate inhibition of folate-dependent enzymes of purine nucleotide biosynthesis

Academic Article


  • 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). The K(i) values for MTX and 7-OH-MTX for avian liver 5-aminoimidazole-4-carboxamide ribonucleotide transformylase differ by 4.5-fold in favour of 7-OH-MTX as the better inhibitor, while K(i) 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.
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    Digital Object Identifier (doi)

    Author List

  • Baggott JE; Morgan SL; Vaughn WH
  • Start Page

  • 627
  • End Page

  • 629
  • Volume

  • 300
  • Issue

  • 3