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
Adjuvant doxorubicin and cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy in premenopausal women with axillary lymph node positive breast carcinoma.
2000 Dec 15
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.
2001 May
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
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
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 Tue Mar 06 10:30:20 UTC 2018
Edited
by admin
on Tue Mar 06 10:30:20 UTC 2018
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
R-METHOTREXATE
USP-RS  
Common Name English
METHOTREXATE [INN]
Common Name English
METHOTREXATUM [WHO-IP LATIN]
Common Name English
METHOTREXATE [USAN]
Common Name English
AMETHOPTERIN
Common Name English
XATMEP
Brand Name English
METHOTREXATE [MART.]
Common Name English
R-METHOTREXATE [USP-RS]
Common Name 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
LIVERTOX 619
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-VATC QL01BA01
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-ESSENTIAL MEDICINES LIST 8.2
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-ATC L01BA01
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
NDF-RT N0000175584
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-VATC QL04AX03
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
NDF-RT N0000000111
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-ATC L04AX03
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
WHO-ESSENTIAL MEDICINES LIST 2.4
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
Code System Code Type Description
LactMed
59-05-2
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
ChEMBL
CHEMBL34259
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
RXCUI
6851
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY RxNorm
MERCK INDEX
M7327
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY Merck Index
PUBCHEM
126941
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY SWITZERF
DRUG BANK
DB00563
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
ECHA (EC/EINECS)
200-413-8
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
HSDB
59-05-2
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
CAS
59-05-2
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
IUPHAR
4815
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
METHOTREXATE
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
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 Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
INN
926
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
WIKIPEDIA
METHOTREXATE
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
UCSF-FDA TRANSPORTAL
Methotrexate
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
MESH
D008727
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
NCI_THESAURUS
C642
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
EVMPD
SUB08856MIG
Created by admin on Tue Mar 06 10:30:20 UTC 2018 , Edited by admin on Tue Mar 06 10:30:20 UTC 2018
PRIMARY
Related Record Type Details
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
EP
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
TRANSPORTER -> SUBSTRATE
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