Methotrexate MTX

Widely used, MTX is effective in:

♦ Breast cancer

♦ Osteogenic sarcoma



Elimination deed dTMP






TS MTXH|C [DHFR] inhibitors

MTX Cytotoxics (MTX-methotrexate; 5-FU -5-fluorouracil;TS

inhibitors include ralitrexed) dTTP Normal metabolites -X Indicates enzyme inhibition

[DHPD) Enzyme (TS—thymidylate synthase; DHPD—dihydropyrimidine dehydrogenase; DHFR—dihydrofolate reductase)

Main sites of action of anti-metabolites.

♦ Bladder carcinoma

♦ Gastric cancer

♦ Choriocarcinoma

♦ Head and neck cancers

Also used for psoriasis and rheumatoid arthritis, MTX is actively transported into cells where it is polyglutamated, binds tightly to and inhibits DHFR. It also:

♦ Inhibits other enzymes e.g. TS

♦ Impairs DNA repair

♦ Causes accumulation of dihydrofolate polyglutamates (that in turn inhibit folate-dependent enzymes)

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