Drug ID:Drug64
Drug Name:Methotrexate
CID:126941
DrugBank ID:DB00563
Modality:Small Molecule
Groups:approved
US Approved:YES
Other Approved:YES
Identifier: NCT00035074, , NCT02413047, , NCT01393405, , NCT00498589
Molecular Formula:C20H22N8O5
Molecular Weight:454.4 g/mol
Isomeric SMILES:CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O
Synonyms:methotrexate; 59-05-2; Rheumatrex; Amethopterin; Methylaminopterin; Metatrexan; Hdmtx; Ledertrexate; Methylaminopterinum; MTX
Phase 0: 18
Phase 1: 204
Phase 2: 717
Phase 3: 465
Phase 4: 225
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]

Molecular Structure

2D Molecular Structure

Knowledge Graph

dtIDCIDCompound NameGene IDGene NameSpeciesPubMed IDsAction
dt570 126941 Methotrexate 3417 IDH1 Homo sapiens (human) None
dt571 126941 Methotrexate 1014 CDH16 Homo sapiens (human) Inhibitor
dt572 126941 Methotrexate 10919 EHMT2 Homo sapiens (human) None
dt573 126941 Methotrexate 5423 POLB Homo sapiens (human) None
dt574 126941 Methotrexate 93777387 folA Escherichia coli K-12 16873019 None
dt575 126941 Methotrexate 1719 DHFR Homo sapiens (human) 12872145 DHFR protein polymorphism results in decreased susceptibility to folic acid antagonists
dt576 126941 Methotrexate 2940 GSTA3 Rattus norvegicus (Norway rat) 12872145 GSTA3 protein results in decreased susceptibility to folic acid antagonists
dt577 126941 Methotrexate 23435 TARDBP Homo sapiens (human) None
dt578 126941 Methotrexate 4780 NFE2L2 Homo sapiens (human) None

  • No data available

Phase Distribution
Phase Description
  • Phase 0: Exploratory trials to assess drug behavior in humans
  • Phase 1: Safety trials to determine safe dosage range
  • Phase 2: Efficacy trials to evaluate therapeutic effects
  • Phase 3: Large-scale trials to confirm efficacy and safety
  • Phase 4: Post-marketing surveillance for long-term safety and efficacy

Trial IDTitlePhaseStatusSponsorIndicationsInterventions
NCT00498589 Comparison of Methotrexate vs Placebo in Corticosteroid-dependent Ulcerative Colitis PHASE2 COMPLETED Centre Hospitalier Universitaire de Besancon Ulcerative Colitis DRUG: methotrexate|DRUG: placebo Details
NCT01393405 Methotrexate in Induction and Maintenance of Steroid Free Remission in Ulcerative Colitis PHASE2 COMPLETED University of North Carolina, Chapel Hill Ulcerative Colitis DRUG: Methotrexate Details
NCT04205734 Methotrexate Polyglutamate Measurements in Patients With Inflammatory Bowel Disease None SUSPENDED Boston Children's Hospital IBD DIAGNOSTIC_TEST: MTX Assessment Details
NCT04196920 Methotrexate-associated Anti-TNF Combination Therapy, the Neglected One ! None UNKNOWN University Hospital, Montpellier Chronic Inflammatory Bowel Disease None Details
NCT00035074 A Pharmacokinetic Study to Determine the Oral Bioavailability of Methotrexate in Patients With Inflammatory Bowel Disease None COMPLETED National Center for Research Resources (NCRR) Inflammatory Bowel Disease DRUG: Methotrexate Details
NL-OMON48064 Methotrexate to suppress immunogenicity to anti-tumor necrosis factor therapy in IBD patients with loss of response - Immunix Not Available None Academisch Medisch Centrum Inflammatory Bowel Disease (Crohn's Disease and U… Addition of methotrexaat to anti-therapy (inflixi… Details
NCT03860012 Evaluating the Efficacy of Weekly Folic Acid in Pediatric Inflammatory Bowel Disease Patients on Methotrexate PHASE4 Recruiting Le Bonheur Children's Hospital Inflammatory Bowel Diseases Drug: Folic Acid Details
NCT03204136 Tacrolimus Versus Methotrexate as Rescue Therapy for Refractory Inflammatory Bowel Disease: an Open-label, Retrospective Study Not Available Not recruiting Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, China Inflammatory Bowel Diseases;Inflammatory Bowel Di… None Details
ISRCTN23541842 The auxiliary diagnostic value of fissured tongue on axial and peripheral joint dysfunction in Ankylosing Spondylitis Not Available Not Recruiting Zhejiang University Of Chinese Medicine Ankylosing spondylitis Musculoskeletal Diseases … Participants are screened and undergo a clinical … Details
NCT03531593 Dose Effect Relationship of Methotrexate and Hepatic Fibrosis in Patients With Inflammatory Bowel Disease Not Available Not recruiting Children's Mercy Hospital Kansas City Inflammatory Bowel Diseases;Liver Fibroses;Methot… Diagnostic Test: Ultrasound Elastography Details
EUCTR2016-000522-18-FR Risk stratified randomized controlled trial in paediatric Crohn Disease: Methotrexate versus azathioprine or adalimumab for maintaining remission in patients at low or at high risk for aggressive disease course, respectively a treatment strategy - REDUCE-RISKincd-PIBD-TRIAL PHASE4 Not Available PIBDNet Crohn disease;Therapeutic area: Diseases [C] - Di… Product Name: humira Pharmaceutical Form: Solutio… Details
NCT02461784 The Effect of Methotrexate on Sperm Quality in Men With Inflammatory Bowel Disease None TERMINATED University of Wisconsin, Madison Inflammatory Bowel Disease (IBD) PROCEDURE: Semen & Data Collection Details
NCT05927064 Study Evaluating the Persistence, Efficacy and Tolerability of Methotrexate in Inflammatory Bowel Disease Patients None COMPLETED Central Hospital, Nancy, France Inflammatory Bowel Diseases|Crohn Disease|Ulcerat… None Details
NCT02413047 Evaluate if Response to Infliximab or Adalimumab May be Regained With an Immunomodulator None TERMINATED Indiana University Inflammatory Bowel Disease|Ulcerative Colitis|Cro… DRUG: Azathioprine|DRUG: 6 mercaptopurine|DRUG: M… Details
NCT01716039 Pharmacokinetics of Adalimumab With Methotrexate for Treatment of Patients With Ulcerative Colitis (UC) PHASE2 TERMINATED Alimentiv Inc. Ulcerative Colitis DRUG: MTX 12.5|DRUG: MTX 25|DRUG: Adalimumab Details

Disease IDDisease NameDefinitionCategoryRelated DrugsMechanism
No data available

Strategy IDTherapeutic StrategySynonymsRelated DrugsMechanism
S02 Immunosuppression Classic immunosuppressive drugs azathioprine; 6-mercaptopurine; methotrexate; ciclosporin-A; tacrolimus Ciclosporin-A and tacrolimus bind to specific intracellular… Details

Combating Methotrexate Resistance in Cancer Treatment: A Review on Navigating P…

PMID: 40270992
Year: 2025
Relationship Type: Treatment Score: 7.5

Methotrexate (MTX), a potent analogue and antagonist of folic acid, is a first-line treatment for rheumatoid arthritis, IBD and cancer. The developme…

Erythrocyte Methotrexate-Polyglutamate Concentrations in Pediatric Inflammatory…

PMID: 39982703
Year: 2025
Relationship Type: Treatment Score: 7.5

BACKGROUND AND AIMS: Therapeutic drug monitoring (TDM) of methotrexate (MTX) is challenging due to its pharmacokinetics and short plasma half-life. I…

Effectiveness and Tolerability of Methotrexate Combined with Biologics in Patie…

PMID: 38217678
Year: 2024
Relationship Type: Treatment Score: 7.5

BACKGROUND: Methotrexate (MTX) combination therapy with biological agents has gained increasing interest. Here, we assessed the efficacy and tolerabi…

Oral Versus Subcutaneous Methotrexate in Immune-Mediated Inflammatory Disorders…

PMID: 37768405
Year: 2023
Relationship Type: Treatment Score: 7.5

PURPOSE: This review aims to critically evaluate the potential benefit of either oral or subcutaneous administration of methotrexate (MTX) in various…

Therapeutic drug monitoring of methotrexate in patients with Crohn's disease

PMID: 37767910
Year: 2023
Relationship Type: Treatment Score: 7.5

BACKGROUND: Therapeutic drug monitoring (TDM) has the potential to improve efficacy and diminish side effects. Measuring methotrexate-polyglutamate (…

Colon-specific delivery of methotrexate using hyaluronic acid modified pH-respo…

PMID: 36804523
Year: 2023
Relationship Type: Treatment Score: 7.5

Oral immunosuppressant methotrexate (MTX) is an effective method for the treatment of inflammatory bowel disease (IBD). To overcome the defects of cl…

The Effectiveness and Safety of Methotrexate as the First-Line Immunomodulator …

PMID: 36754081
Year: 2023
Relationship Type: Treatment Score: 7.5

OBJECTIVES: Methotrexate (MTX) has been used as maintenance therapy for Crohn disease (CD) in adults and children. However, there are only a few stud…

A meta-analysis of methotrexate polyglutamates in relation to efficacy and toxi…

PMID: 36326810
Year: 2023
Relationship Type: Treatment Score: 7.5

AIMS: In immune-mediated inflammatory diseases (IMIDs), early symptom control is a key therapeutic goal. Methotrexate (MTX) is the first-line treatme…

Subcutaneous administration, higher age and lower renal function are associated…

PMID: 35907797
Year: 2022
Relationship Type: Treatment Score: 7.5

BACKGROUND: Methotrexate is an immunomodulatory drug for patients with Crohn's disease. Erythrocyte MTX-polyglutamates (MTX-PG(1-5)) may be used for …

Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease …

PMID: 35758420
Year: 2022
Relationship Type: Treatment Score: 7.5

OBJECTIVES: Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to asses…

Mucosal healing with methotrexate versus azathioprine treatment in pediatric Cr…

PMID: 35373937
Year: 2022
Relationship Type: Treatment Score: 7.5

BACKGROUND/OBJECTIVES: The current treatment goal for inflammatory bowel disease (IBD) is achievement of mucosal healing (MH). While established with…

Short-term tolerability and effectiveness of methotrexate monotherapy in adult …

PMID: 34539814
Year: 2021
Relationship Type: Treatment Score: 7.5

INTRODUCTION: Immunomodulators remain fundamental for the medical treatment of Crohn's disease (CD). Methotrexate (MTX) is widely used as a second-li…

Cost-Effectiveness Analysis of Parenteral Methotrexate for the Treatment of Cro…

PMID: 33426625
Year: 2021
Relationship Type: Treatment Score: 7.5

BACKGROUND: Despite worldwide use of parenteral methotrexate (pMTX), health economic evidence for its use in Crohn's disease (CD) is limited. The low…

Pharmacogenetic studies of thiopurine methyltransferase genotype-phenotype conc…

PMID: 32865889
Year: 2021
Relationship Type: Treatment Score: 7.5

The discovery and implementation of thiopurine methyltransferase (TPMT) pharmacogenetics has been a success story and has reduced the suffering from …

Protocol for a multinational risk-stratified randomised controlled trial in pae…

PMID: 32611737
Year: 2020
Relationship Type: Treatment Score: 7.5

INTRODUCTION: Immunomodulators such as thiopurines (azathioprine (AZA)/6-mercaptopurine (6MP)), methotrexate (MTX) and biologics such as adalimumab (…

How does methotrexate work?

PMID: 32239204
Year: 2020
Relationship Type: Treatment Score: 7.5

Developed over 70 years ago as an anti-folate chemotherapy agent, methotrexate (MTX) is a WHO 'essential medicine' that is now widely employed as a f…

Analytical methodologies for determination of methotrexate and its metabolites …

PMID: 31890337
Year: 2019
Relationship Type: Treatment Score: 7.5

Methotrexate (MTX) is a folate antagonist drug used for several diseases, such as cancers, various malignancies, rheumatoid arthritis (RA) and inflam…

[Successful treatment of gangrenous pyoderma with methotrexate in a patient wit…

PMID: 31333236
Year: 2019
Relationship Type: Treatment Score: 7.5

Pyoderma gangrenosum (PG) is a neutrophilic, cutaneous-ulcerative, non-infectious dermatosis that occurs in up to 2% of patients with Crohn's disease…

A single-center experience with methotrexate in the treatment of Chinese Crohn'…

PMID: 30516330
Year: 2018
Relationship Type: Treatment Score: 7.3

OBJECTIVE: Methotrexate (MTX) can be used as an alternative for patients with Crohn's disease (CD) who are intolerant of thiopurine. This retrospecti…

Methotrexate and Thioguanine Rescue Therapy for Conventional Thiopurine Failing…

PMID: 29668998
Year: 2018
Relationship Type: Treatment Score: 7.3

BACKGROUND: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accept…

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