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59-05-2 molecular structure
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(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid

ChemBase ID: 445
Molecular Formular: C20H22N8O5
Molecular Mass: 454.43928
Monoisotopic Mass: 454.17131584
SMILES and InChIs

SMILES:
OC(=O)[C@@H](NC(=O)c1ccc(N(Cc2nc3c(nc2)nc(nc3N)N)C)cc1)CCC(=O)O
Canonical SMILES:
OC(=O)CC[C@@H](C(=O)O)NC(=O)c1ccc(cc1)N(Cc1cnc2c(n1)c(N)nc(n2)N)C
InChI:
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
InChIKey:
FBOZXECLQNJBKD-ZDUSSCGKSA-N

Cite this record

CBID:445 http://www.chembase.cn/molecule-445.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
IUPAC Traditional name
methotrexate
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
Brand Name
Abitrexate
Antifolan
Arbitrexate
Emtexate
Folex
Ledertrexate
Metatrexan
Methotrate
Mexate
Rheumatrex
Trexall
Synonyms
N-[4-[[(2,4-Diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic Acid
(+)-Amethopterin
4-Amino-N10-methylpteroylglutamic Acid
4-Amino-N10-methylfolic Acid
Antifolan
CL 14377
EMT 25299
Emtexate
Ledertrexate
L-Metatrexan
Mexate
NSC 740
R 9985
MTX
N-Bismethylpteroylglutamic Acid
Methylaminopterinum
Methylaminopterin
Methotrexate Sodium
Amethopterin
Amethopterine
HDMTX
L-Amethopterin
Methopterin
Methotextrate
Methotrexat
Methotrexate
Methotrexate
Rheumatrex
Trexall
Abitrexate(Methotrexate)
(S)-2-(4-(((2,4-Diaminopteridin-6-yl)methyl)(methyl)amino)benzamido)pentanedioic acid
Extexate
Maxtrex
Methotrexate
(2S)-2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid
CAS Number
59-05-2
MDL Number
MFCD00150847
MFCD00064370
PubChem SID
160963908
46507678
PubChem CID
126941
CHEBI ID
44185
ATC CODE
L04AX03
L01BA01
CHEMBL
34259
Chemspider ID
112728
DrugBank ID
DB00563
KEGG ID
D00142
Unique Ingredient Identifier
YL5FZ2Y5U1
Wikipedia Title
Methotrexate
Medline Plus
a682019

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem ALOGPS 2.1
Acid pKa 3.2608347  H Acceptors 12 
H Donor LogD (pH = 5.5) -3.6408224 
LogD (pH = 7.4) -6.5636883  Log P -0.23645228 
Molar Refractivity 119.2108 cm3 Polarizability 43.521362 Å3
Polar Surface Area 210.54 Å2 Rotatable Bonds
Lipinski's Rule of Five false 
Log P -0.91  LOG S -3.42 
Solubility (Water) 1.71e-01 g/l 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
2600 mg/L expand Show data source
DMSO expand Show data source
Apperance
Yellow Solid expand Show data source
Melting Point
>188°C (dec.) expand Show data source
195 - 197°C expand Show data source
Hydrophobicity(logP)
-1.427 expand Show data source
-2.2 expand Show data source
Storage Condition
-20°C expand Show data source
Refrigerator expand Show data source
Storage Warning
Hygroscopic expand Show data source
MSDS Link
Download expand Show data source
Target
Antimetabolite expand Show data source
Admin Routes
oral, IV, IM, SC, intrathecal expand Show data source
Bioavailability
17–90% expand Show data source
Excretion
renal 48–100% expand Show data source
Half Life
15 hours (dose dependent) expand Show data source
Metabolism
hepatic expand Show data source
Legal Status
POM (UK) expand Show data source
Rx-only (US) expand Show data source
S4 (Australia) expand Show data source
Pregnancy Category
D (Australia) expand Show data source
X (US) expand Show data source
Mechanism of Action
Dihydrofolate reductase inhibitor expand Show data source
Purity
95% expand Show data source
95+% expand Show data source
98% expand Show data source
Salt Data
Free Base expand Show data source
Certificate of Analysis
Download expand Show data source
Application(s)
Antineoplastic and antipsoriatic agent expand Show data source
Used in the treatment of rheumatoid arthritis. expand Show data source

DETAILS

DETAILS

DrugBank DrugBank Selleck Chemicals Selleck Chemicals Wikipedia Wikipedia TRC TRC
DrugBank - DB00563 external link
Item Information
Drug Groups approved
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]
Indication For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis.
Pharmacology 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 also indicated in the management of severe, active, classical, or definite rheumatoid arthritis.
Toxicity Symptoms of overdose include bone marrow suppression and gastrointestinal toxicity. LD50=43mg/kg(orally in rat).
Affected Organisms
Humans and other mammals
Biotransformation Hepatic.
Absorption Generally well absorbed with a mean bioavailability of about 60%.
Half Life Low doses: 3 to 10 hours; High doses: 8 to 15 hours.
Protein Binding 50%, primarily to albumin
Elimination With IV administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose.
Distribution * 0.4 to 0.8 L/kg
References
Klareskog L, van der Heijde D, de Jager JP, Gough A, Kalden J, Malaise M, Martin Mola E, Pavelka K, Sany J, Settas L, Wajdula J, Pedersen R, Fatenejad S, Sanda M: Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet. 2004 Feb 28;363(9410):675-81. [Pubmed]
Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H: The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. [Pubmed]
External Links
Wikipedia
RxList
PDRhealth
Drugs.com
Selleck Chemicals - S1210 external link
Research Area: Immunology
Biological Activity:
Abitrexate(Methotrexate) is an antimetabolite and antifolate agent with antineoplastic and immunosuppressant activities. Methotrexate competitively and irreversibly inhibits dihydrofolate reductase (DHFR), resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses. Methotrexate also exhibits potent immunosuppressant activity although the mechanism(s) of actions is unclear. [1,2] In a panel of six pediatric leukemia and lymphoma cell lines, this drug performed growth inhibitory activity with median IC50 78 nM. [3]
Toronto Research Chemicals - M260675 external link
A Folic acid antagonist. Used as a antineoplastic and antirheumatic.

REFERENCES

REFERENCES

From Suppliers Google Scholar IconGoogle Scholar PubMed iconPubMed Google Books IconGoogle Books
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  • • Johnston A, Gudjonsson JE, Sigmundsdottir H, Ludviksson BR, Valdimarsson H: The anti-inflammatory action of methotrexate is not mediated by lymphocyte apoptosis, but by the suppression of activation and adhesion molecules. Clin Immunol. 2005 Feb;114(2):154-63. Pubmed
  • • http://en.wikipedia.org/wiki/Methotrexate
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