U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H22N8O5
Molecular Weight 454.4393
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of METHOTREXATE

SMILES

CN(CC1=NC2=C(N)N=C(N)N=C2N=C1)C3=CC=C(C=C3)C(=O)N[C@@H](CCC(O)=O)C(O)=O

InChI

InChIKey=FBOZXECLQNJBKD-ZDUSSCGKSA-N
InChI=1S/C20H22N8O5/c1-28(9-11-8-23-17-15(24-11)16(21)26-20(22)27-17)12-4-2-10(3-5-12)18(31)25-13(19(32)33)6-7-14(29)30/h2-5,8,13H,6-7,9H2,1H3,(H,25,31)(H,29,30)(H,32,33)(H4,21,22,23,26,27)/t13-/m0/s1

HIDE SMILES / InChI

Molecular Formula C20H22N8O5
Molecular Weight 454.4393
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

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 indicated in the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. In acute lymphocytic leukemia, methotrexate is indicated in the prophylaxis of meningeal leukemia and is used in maintenance therapy in combination with other chemotherapeutic agents. Methotrexate is also indicated in the treatment of meningeal leukemia. Methotrexate is used alone or in combination with other anticancer agents in the treatment of breast cancer, epidermoid cancers of the head and neck, advanced mycosis fungoides (cutaneous T cell lymphoma), and lung cancer, particularly squamous cell and small cell types. Methotrexate is also used in combination with other chemotherapeutic agents in the treatment of advanced stage non-Hodgkin’s lymphomas. Methotrexate is indicated in the symptomatic control of severe, recalcitrant, disabling psoriasis. Methotrexate is indicated in the management of selected adults with severe, active rheumatoid arthritis (ACR criteria), or children with active polyarticular-course juvenile rheumatoid arthritis.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
[Carboxypeptidase-G2-rescue in a woman with methotrexate-induced renal failure].
2000 Aug 15
Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study.
2000 Dec
Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.
2000 Dec 15
Veno-occlusive disease of the liver associated with thiopurines in a child with acute lymphoblastic leukemia.
2000 Jul-Aug
Leukocytoclastic vasculitis associated with methotrexate therapy.
2000 Jul-Sep
Serious liver disease in a patient receiving methotrexate and leflunomide.
2000 Nov
Expression and characterization of recombinant human-derived Pneumocystis carinii dihydrofolate reductase.
2000 Nov
Toxicity of methotrexate treatment in psoriasis and psoriatic arthritis--short- and long-term toxicity in 104 patients.
2001
[Conservative therapy in endocrine orbitopathy: "State of the art"].
2001
Stereoselectivity of the folate transporter in rabbit small intestine: studies with amethopterin enantiomers.
2001
Hospital resources used for ectopic pregnancy treatment by laparoscopy and methotrexate.
2001 Apr-Jun
Randomized, double-blind, crossover, placebo-controlled trial of intravenous ondansetron for the prevention of intrathecal chemotherapy-induced vomiting in children.
2001 Dec
Transient posterior encephalopathy induced by chemotherapy in children.
2001 Feb
[Listeria arthritis in chronic polyarthritis during low dose prednisolone and methotrexate therapy. Case report and review of the literature].
2001 Feb
A comparison of methods of loco-regional chemotherapy combined with systemic chemotherapy as neo-adjuvant treatment of osteosarcoma of the extremity.
2001 Feb
Neoadjuvant chemotherapy for high grade osteosarcoma of the extremities: long-term results for patients treated according to the Rizzoli IOR/OS-3b protocol.
2001 Feb
The value of amino-terminal propeptide of type III procollagen in routine screening for methotrexate-induced liver fibrosis: a 10-year follow-up.
2001 Jan
A clinical study to determine the efficacy and safety of 1% methotrexate/Azone (MAZ) gel applied topically once daily in patients with psoriasis vulgaris.
2001 Jul
[Fatal outcome of a multisystemic sarcoidosis in a 54-year-old patient].
2001 Jul
Long-term cerebral metabolite changes on proton magnetic resonance spectroscopy in patients cured of acute lymphoblastic leukemia with previous intrathecal methotrexate and cranial irradiation prophylaxis.
2001 Jul 1
Relationship between dose-intensity of treatment and outcome for patients with osteosarcoma of the extremity treated with neoadjuvant chemotherapy.
2001 Jul-Aug
[Methotrexate, liver and rheumatoid arthritis in tropical areas].
2001 Jul-Sep
Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure.
2001 Jun
Homocysteine modulation as a reason for continuous folic acid supplementation in methotrexate-treated rheumatoid arthritis patients.
2001 Jun
Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials.
2001 Mar
Inappropriate medical management of spinal epidural abscess.
2001 Mar
Neoadjuvant chemotherapy for osteosarcoma of the extremity: long-term results of the Rizzoli's 4th protocol.
2001 Nov
Tamoxifen-based treatment induces clinically meaningful responses in multiple myeloma patients with relapsing disease after autotransplantation.
2001 Nov-Dec
[Meningeal carcinomatosis as the first manifestation of gastric adenocarcinoma].
2001 Oct 11
Mutation of Trp1254 in the multispecific organic anion transporter, multidrug resistance protein 2 (MRP2) (ABCC2), alters substrate specificity and results in loss of methotrexate transport activity.
2001 Oct 12
Methylation-dependent silencing of the reduced folate carrier gene in inherently methotrexate-resistant human breast cancer cells.
2001 Oct 26
Isolation of rat dihydrofolate reductase gene and characterization of recombinant enzyme.
2001 Sep
Neurotoxicity with leukoencephalopathy after a single intravenous high dose of methotrexate in a patient with lymphoma.
2002
Multiple anomalies in a fetus exposed to low-dose methotrexate in the first trimester.
2002 Apr
Methotrexate leukoencephalopathy presenting as Klüver-Bucy syndrome and uncinate seizures.
2002 Apr
Methotrexate-induced nephrogenic diabetes insipidus: first case report.
2002 Feb
Methotrexate-induced systemic vasculitis.
2002 Feb
Leukemic leptomeningeal involvement in stage 0 and stage 1 chronic lymphocytic leukemia.
2002 Jan
Methotrexate-related nonnecrotizing multifocal axonopathy detected by beta-amyloid precursor protein immunohistochemistry.
2002 Jan
High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma.
2002 Jan
Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice.
2002 Jul
CYP3A4 induction by drugs: correlation between a pregnane X receptor reporter gene assay and CYP3A4 expression in human hepatocytes.
2002 Jul
Oral methotrexate for treatment of ectopic pregnancy.
2002 Jun
Radiation myelitis in a 5-year-old girl.
2002 Mar
CT and MRI appearances of methotrexate leucoencephalopathy.
2002 Mar
[A case of subacute transient cerebral dysfunction in a osteosarcoma patient following high-dose methotrexate].
2002 Mar
Nephrotoxicity due to intermediate-dose methotrexate without rescue in an obese adolescent with acute lymphoblastic leukemia.
2002 Mar
Quantitative MRI assessment of leukoencephalopathy.
2002 May
CNS late-effects after ALL therapy in childhood. Part III: neuropsychological performance in long-term survivors of childhood ALL: impairments of concentration, attention, and memory.
2002 May
Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol.
2002 May
Patents

Sample Use Guides

In Vivo Use Guide
Usual Adult Dose for Acute Lymphoblastic Leukemia Induction: 3.3 mg/m2/day orally or IM (in combination with prednisone 60 mg/m2) daily Usual Adult Dose for Psoriasis Single Dose: 7.5 mg/week orally, IM, or IV until adequate response is achieved Divided Dose: 2.5 mg orally, IM, or IV every 12 hours for 3 doses once a week Maximum weekly dose: 20 mg
Route of Administration: oral, IM, IV or subcutaneous
In Vitro Use Guide
VEGF and Ang-1 levels were significantly lower, and Ang-2 levels were significantly higher in NPs (organ-cultured nasal polyps) treated with 100-umolar Methotrexate than in nontreated NPs
Substance Class Chemical
Created
by admin
on Mon Oct 21 20:39:11 UTC 2019
Edited
by admin
on Mon Oct 21 20:39:11 UTC 2019
Record UNII
YL5FZ2Y5U1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
METHOTREXATE
EP   HSDB   INN   MART.   MI   USAN   USP   VANDF   WHO-DD   WHO-IP  
INN   USAN  
Official Name English
METHOTREXATE [WHO-IP]
Common Name English
METHYLAMINOPTERIN
Common Name English
METHOTREXATE [INN]
Common Name English
METHOTREXATUM [WHO-IP LATIN]
Common Name English
METHOTREXATE [IARC]
Common Name English
METHOTREXATE [USAN]
Common Name English
AMETHOPTERIN
Common Name English
XATMEP
Brand Name English
METHOTREXATE [MART.]
Common Name English
ADX-2191
Code English
METHOTREXATE [MI]
Common Name English
R-9985
Code English
METHOTREXATE [EP]
Common Name English
CL-14377
Code English
EMT-25299
Code English
METHOTREXATE [HSDB]
Common Name English
MTX
Common Name English
RASUVO
Brand Name English
METHOTREXATE [WHO-DD]
Common Name English
CL 14377
Code English
NSC-740
Code English
METHOTREXATE [JAN]
Common Name English
METHOTREXATE [USP]
Common Name English
(2S)-2-((4-(((2,4-DIAMINOPTERIDIN-6-YL)METHYL)(METHYL)AMINO)BENZOYL)AMINO)PENTANEDIOIC ACID
Systematic Name English
METHOTREXATE [VANDF]
Common Name English
Classification Tree Code System Code
IARC Methotrexate
FDA ORPHAN DRUG 469315
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
LIVERTOX 619
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 440314
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-VATC QL01BA01
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 479515
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
NCI_THESAURUS C511
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 76693
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-ATC L01BA01
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
NDF-RT N0000175584
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
NCI_THESAURUS C2153
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
EU-Orphan Drug EU/3/07/495
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 286409
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 479615
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-VATC QL04AX03
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
NDF-RT N0000000111
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-ATC L04AX03
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 43389
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 2.4
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
FDA ORPHAN DRUG 630518
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
Code System Code Type Description
LactMed
59-05-2
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
ChEMBL
CHEMBL34259
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
RXCUI
6851
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M7327
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY Merck Index
PUBCHEM
126941
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
DRUG BANK
DB00563
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
ECHA (EC/EINECS)
200-413-8
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
HSDB
59-05-2
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
CAS
59-05-2
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
IUPHAR
4815
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
METHOTREXATE
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY Description: A yellow to orange, crystalline powder. Solubility: Practically insoluble in water, ethanol (~750 g/l) TS, dichloroethane R, and ether R; very soluble in diluted solutions of alkali hydroxides and carbonates. Category: Cytotoxic drug.Storage: Methotrexate should be kept in a tightly closed container, protected from light. Additional information: Methotrexate is gradually affected by light. CAUTION: Methotrexate must be handled with care, avoiding contact with the skin and inhalation of airborne particles. Definition: Methotrexate contains not less than 96.0% and not more than 102.0% of C20H22N8O5, calculated with reference to the anhydrous substance.
EPA CompTox
59-05-2
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
INN
926
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
WIKIPEDIA
METHOTREXATE
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
UCSF-FDA TRANSPORTAL
Methotrexate
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
MESH
D008727
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
NCI_THESAURUS
C642
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
EVMPD
SUB08856MIG
Created by admin on Mon Oct 21 20:39:12 UTC 2019 , Edited by admin on Mon Oct 21 20:39:12 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
SALT/SOLVATE -> PARENT
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TARGET -> INHIBITOR
RACEMATE -> ENANTIOMER
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
Related Record Type Details
METABOLITE -> PARENT
METABOLITE INACTIVE -> PARENT
URINE
METABOLITE TOXIC -> PARENT
7-OH-MTX levels were correlated with nephrotoxicity in adolescents.
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 1.4
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
If present, methotrexate dimethylamide and Methotrexate related compound I may not be completely resolved by the method. These peaks are integrated together to determine conformance (NMT 0.2%)
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
For the calculation of contents, multiply the peak areas by 0.8
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
UNSPECIFIED
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC Elimination
PHARMACOKINETIC
Population
PHARMACOKINETIC
Elimination
PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC Steady state
PHARMACOKINETIC
Initial
PHARMACOKINETIC