Figure 1.

Simplified scheme of cellular pathway and the targets of MTX. MTX enters the cell trough RFC1. After that, MTX inhibits DHFR, TYMS, ATIC. This anti-leukemic drug is pumped from the cell by means of membrane transporters (ABC)

Abbreviations: ABC: ATP-binding cassette; ATIC: 5-aminoimidazole-4-carboxamide ribonucleotide transformylase; DHF: Dihydrofolate; dTMP: deoxythymidine-50-monophosphate; dUMP: deoxyurindine-50-monophosphate Methyl-THF: 5-methyl-tetrahydrofolate; Methylene-THF: 5, 10-methylene-tetrahydrofolate; MTX: Methotrexate; MTX-PG: MTX polyglutamates; MS: Methionine synthase; RFC1: Replication factor C subunit 1; SHMT: Serine hydroxymethyl transferase; THF: Tetrahydrofolate; TS: Thymidylate synthase; TYMS: Thymidylate synthase