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Description: An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of tetrahydrofolate dehydrogenase and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA. [PubChem]
Drug Type: Small Molecule; Approved
Pharmacology: Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the 'S' phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis.
Mechanism of Action: Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known.
Indication: For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis.
Half Life: Low doses: 3 to 10 hours; High doses: 8 to 15 hours.
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Data Correlations | 8 studies

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Genes category icon Genes
Score Help
DHFR 100 100
CDC20 88 88
KLHL20 82 82
VEGFA 82 82
CCNB1 79 79
HMMR 78 78
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Biogroups category icon Biogroups
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Ubiquitin-conjugating enzyme, E2 100 100
RNA recognition motif, RNP-1 100 100
Nucleotide-binding, alpha-beta plai… 100 100
Nucleotide Metabolism 100 100
Ubiquitin-conjugating enzyme/RWD-li… 100 100
Cell Cycle 99 99
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Individual Studies

  • Methotrexate-resistant leukemia T-cells

    Homo sapiens Homo sapiens | RNA Expression   RNA Expression

    To compare the pattern of Gene expression by 7-hydroxymethotrexate-resistant human leukemia cells reveals changes designed to preserve intracellular levels of folate and nucleotide biosynthesis. We used microarrays to detail the global programme of gene expression underlying cellularisation and iden…

    Authors: Fotoohi K, Moshfegh A, Albertioni F

    Organization: Karolinska Institutet Oncology and Patho…

  • HT29 cells sensitive and resistant to methotrexate

    Homo sapiens Homo sapiens | RNA Expression   RNA Expression

    The abstract of the associated publication (Selga E, Noé V, Ciudad CJ. Biochemical Pharmacology 2007 Sep 8; Article in press) is the following:

    Authors: Selga Elisabet, Ciudad J Carlos, Noé Veronique

    Organization: university of barcelona biochemistry and…
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Associated Researchers

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Thought leaders and organizations working on research involving methotrexate.

View All Author iconAuthors
  • Paul Emery
  • Murray L Barclay
  • Désirée van der Heijde
  • Peter T Chapman
  • Lisa K Stamp
View All Clinical trial sponsors icon Clinical Trials Sponsors
  • Abbott
  • Radboud University
  • Children's Cancer and Leukaemia Group
  • Assistance Publique - Hôpitaux de Paris
  • Wyeth
View All Affiliations icon Organizations
  • Leiden University Medical Center
  • University of Otago
  • University of Leeds
  • Dana-Farber Cancer Institute
  • Washington University School of Medicine

Clinical Trials | 1,776 trials

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