Methotrexate MTX
Widely used, MTX is effective in:
♦ Breast cancer
♦ Osteogenic sarcoma
-FduMP
Capecitabine
Elimination deed dTMP
dTTP
10-CHO-FH, dUMP
5-CHO-FH4
(Leucovorin)
-FduMP
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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