Drug · Small Molecule

Methotrexate

CI-DRUG-00000377Explore in graph →NCIt C642 CHEMBL34259 CIViC Approved

Regulatory

Approvals (87)

Each record names the authority, jurisdiction, indication text and status. A drug approved in one jurisdiction for one indication is not 'approved' in general.

health-canada-dpdRegulatory50 approval records · authority, jurisdiction and indication text as published.

Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
CA Health Canada	—	Marketed in Canada as PMS-METHOTREXATE TABLETS (DIN 02561956) under ATC L01BA01 METHOTREXATE. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Nov 28, 2025	health-canada-dpd
CA Health Canada	—	Marketed in Canada as JAMP METHOTREXATE TABLETS (DIN 02553740) under ATC L01BA01 METHOTREXATE. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Jun 10, 2025	health-canada-dpd
CA Health Canada	—	Marketed in Canada as M-METHOTREXATE (DIN 02534916) under ATC L01BA01 METHOTREXATE. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Apr 24, 2024

Health Canada records are DIN-level: one row per marketed product (brand, strength, form). The Drug Product Database does not publish indications, so no cancer is stated for these rows, and a cancelled or dormant DIN is the status of that one product — not a withdrawal of the molecule.

Data updated 18 hours agoSource updated unknown

Derived

Development pipeline

Most advanced stage across all cancers, then per top-level cancer reached through trial conditions or approval indications. Approval in any ingested jurisdiction outranks trial phase; counts are interventional studies.

Scope	Stage	Max phase	Active	Recruiting	Phase 3	Trials	Approvals	Jurisdictions	First approval	First trial
All cancers	Approved	Phase 4	128	71	175	719	87	CA, EU, US	Aug 10, 1959	1986-05
Leukemia	Approved	Phase 4	69	36	83	359	9	EU, US	Aug 10, 1959	1986-05
Non-Hodgkin Lymphoma	Approved	Phase 4	39	23	21	135	9	US	Aug 10, 1959	1988-03
Malignant Central Nervous System Neoplasm	Approved	Phase 4	17	10	7	49	1

Curated evidence

Clinical evidence (14)

CIViC items in which this therapy appears, grouped by cancer context, then molecular profile. 50 items per page.

civicCuratedShowing 1–14 of 14 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
NTRK3 Fusion1
Etoposide + Larotrectinib

Clinical trials

Trials with this intervention (728)

Most recently updated first, 50 per page.

clinicaltrialsPublishedShowing 1–50 of 728 studies · status and phase as posted by the registrant; each row links to the study record.

NCT	Title	Status	Phase	Enrollment (n)	Sponsor	Countries	Last update	Source
NCT06124157	A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)	recruiting	Phase 2	222	National Cancer Institute (NCI)NIH	4	Sep 28, 2026	clinicaltrials
NCT03779854	Naive T Cell Depletion for Preventing Chronic Graft-versus-Host Disease in Children and Young Adults With Blood Cancers Undergoing Donor Stem Cell Transplant

Molecule

Record

Kind: Small Molecule
Mechanism: Dihydrofolate reductase inhibitor
Targets: 1 gene
UNII: 3IG1E710ZN
Aliases: 4-Amino-10-methylfolic Acid, 4-Amino-4-deoxy-10-methylpteroyl-L-glutamic Acid, Abitrexate, ACH-METHOTREXATE, ADX-2191, Alpha-Methopterin, Amethopterin, APO-METHOTREXATE, AURO-METHOTREXATE, Brimexate, CL 14377, D-amethopterin, D-methotrexate, Ebetrex, EMT-25299, Emtexate, Emtexate high-pot, Emtexate pf, Emthexat, Emthexate, EUGIA-METHOTREXATE, Farmitrexat, Fauldexato, Folex, Folex PFS, JAMP-METHOTREXATE, Jylamvo, JYLAMVO, Lantarel, Ledertrexate … (+50)

Data updated 21 hours agoSource updated unknown

Identifiers

Codes (107)

Upstream identifiers kept as first-class codes; each links to its registry where a stable public URL exists.

System	Code	Label
ATC (WHO)	L01BA01	METHOTREXATE
ATC (WHO)	L04AX03

IKZF1 Deletion1

Cytarabine + Daunorubicin + Fludarabine + Imatinib + MethotrexateCombination

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Supports Sensitivity Response

accepted

EID7366

This prospective study reports on the prognosis of patients with B-ALL and an IKZF1 deletion and the impact of intensification of treatment in this subgroup. In 50 patients from the MS2003 cohort, th… (full text at CIViC)

PMID 30044693 · Yeoh et al., 2018 · Open in CIViC

civic

PRPS1 A190T1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7928

Lentiviral-mediated overexpression of PRPS1 A190T in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 D183E1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7927

Lentiviral-mediated overexpression of PRPS1 D183E in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 K176N1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7926

Lentiviral-mediated overexpression of PRPS1 K176N in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 L191F1

Asparaginase + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7923

Lentiviral-mediated overexpression of PRPS1 L191F in Reh cells resulted no difference in response to Methotrexate, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS1 overexpres… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 N144S1

Asparaginase + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7930

Lentiviral-mediated overexpression of PRPS1 N144S in Reh cells resulted no difference in response to Methotrexate, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS1 overexpres… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 S103N1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7925

Lentiviral-mediated overexpression of PRPS1 S103N in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 S103T1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7924

Lentiviral-mediated overexpression of PRPS1 S103T in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

PRPS1 T303S1

Asparaginase + Cytarabine + Daunorubicin + MethotrexateSubstitutes

B Lymphoblastic Leukemia/LymphomaCURATED_BROADER

Predictive

Does Not Support Resistance

accepted

EID7929

Lentiviral-mediated overexpression of PRPS1 T303S in Reh cells resulted no difference in response to Methotrexate, Cytarabine, Daunorubicin, or L-Asparginase compared to empty vector and wildtype PRPS… (full text at CIViC)

PMID 25962120 · Li et al., 2015 · Open in CIViC

civic

SLCO1B1 N130D1

Methotrexate

Malignant NeoplasmALIAS

Predictive

Supports Adverse Response

accepted

EID1842

499 children from ALL trials treated with methotrexate were genotyped for 8 SNPs in 5 genes. The SLCO1B1 RS2306283 variant was significantly associated with MTX AUC0-48h and as such associated with in… (full text at CIViC)

PMID 23652803 · Radtke et al., 2013 · Open in CIViC

civic

SLCO1B1 RS41490561

Methotrexate

Malignant NeoplasmALIAS

Predictive

Supports Adverse Response

accepted

EID1841

499 children from ALL trials treated with methotrexate were genotyped for 8 SNPs in 5 genes. The SLCO1B1 rs4149056 variant was significantly associated with MTX AUC0-48h and as such associated with in… (full text at CIViC)

PMID 23652803 · Radtke et al., 2013 · Open in CIViC

civic

TYMS RS347430331

Methotrexate

Malignant NeoplasmALIAS

Predictive

Supports Adverse Response

accepted

EID1843

499 children from ALL trials treated with methotrexate were genotyped for 8 SNPs in 5 genes. The TYMS rs34743033 tandem repeat polymorphism was the only significant predictor of stomatitis in a multip… (full text at CIViC)

PMID 23652803 · Radtke et al., 2013 · Open in CIViC

civic

TP53 R273H1

Doxorubicin + MethotrexateSubstitutes

Osteosarcoma

Predictive

Supports Resistance

accepted

EID7430

Several preclinical studies were testing drug resistance mechanisms of TP53-R273H variant. Saos-2 cells were transfected with TP53-R273H mutation and these cells were used in the study. Using a wester… (full text at CIViC)

PMID 17363498 · Wong et al., 2007 · Open in CIViC

civic