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.

emaRegulatory1 approval record · authority, jurisdiction and indication text as published.

Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
EU EMA	Acute Lymphoblastic Leukemia	In rheumatological and dermatological diseases Active rheumatoid arthritis in adult patients. Polyarthritic forms of active, severe juvenile idiopathic arthritis (JIA) in adolescents and children aged 3 years and over when the response to non-steroidal anti-inflammatory drugs (NSAIDs) has been inadequate. Severe, treatment-refractory, disabling psoriasis which does not respond sufficiently to other forms of treatment such as phototherapy, psoralen and ultraviolet A radiation (PUVA) therapy and retinoids, and severe psoriatic arthritis in adult patients. In oncology Maintenance treatment of acute lymphoblastic leukaemia (ALL) in adults, adolescents and children aged 3 years and over.	approved	Mar 29, 2017	ema

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 19 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	B	Supports Sensitivity Response	4	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

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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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 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	D	Does Not Support Resistance	3	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

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	B	Supports Adverse Response	3	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 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	B	Supports Adverse Response	3	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

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	B	Supports Adverse Response	3	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

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	D	Supports Resistance	3	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

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