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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2014-09-23 05:27:06 UTC
HMDB IDHMDB15288
Secondary Accession NumbersNone
Metabolite Identification
Common NameTrimetrexate
DescriptionA nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against pneumocystis pneumonia in AIDS patients. Myelosuppression is its dose-limiting toxic effect. [PubChem]
Structure
Thumb
Synonyms
  1. TMQ
  2. TMX
  3. Trimetrexato [INN-Spanish]
  4. Trimetrexatum [INN-Latin]
Chemical FormulaC19H23N5O3
Average Molecular Weight369.4176
Monoisotopic Molecular Weight369.180089627
IUPAC Name5-methyl-6-{[(3,4,5-trimethoxyphenyl)amino]methyl}quinazoline-2,4-diamine
Traditional Nametrimetrexate
CAS Registry Number52128-35-5
SMILES
COC1=CC(NCC2=C(C)C3=C(C=C2)N=C(N)N=C3N)=CC(OC)=C1OC
InChI Identifier
InChI=1S/C19H23N5O3/c1-10-11(5-6-13-16(10)18(20)24-19(21)23-13)9-22-12-7-14(25-2)17(27-4)15(8-12)26-3/h5-8,22H,9H2,1-4H3,(H4,20,21,23,24)
InChI KeyNOYPYLRCIDNJJB-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteropolycyclic Compounds
ClassQuinazolines
Sub ClassN/A
Other Descriptors
  • Aromatic Heteropolycyclic Compounds
  • Pyrogallols and Derivatives
Substituents
  • Alkyl Aryl Ether
  • Aminopyrimidine
  • Anisole
  • Phenylmethylamine
  • Polyamine
  • Pyrimidine
  • Toluene
Direct ParentQuinazolines
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Antibiotics
  • Antifungal Agents
  • Antimetabolites, Antineoplastic
  • Antiprotozoals
  • Folic Acid Antagonists
Application
  • Pharmaceutical
Cellular locations
  • Membrane (predicted from logP)
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point215 - 217 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility3.09e-02 g/LNot Available
LogP2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.031 g/LALOGPS
logP2.36ALOGPS
logP2.28ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)17.04ChemAxon
pKa (Strongest Basic)7.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area117.54ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity107.7ChemAxon
Polarizability40.24ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01157
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01157
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-1 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01157
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5381
KEGG Compound IDC11154
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTrimetrexate
NuGOwiki LinkHMDB15288
Metagene LinkHMDB15288
METLIN IDNot Available
PubChem Compound5583
PDB IDNot Available
ChEBI ID119101
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
References
  1. Bertino JR, Zhao SC, Mineishi S, Ercikan-Abali EA, Banerjee D: Use of variants of dihydrofolate reductase in gene transfer to produce resistance to methotrexate and trimetrexate. Prog Exp Tumor Res. 1999;36:82-94. Pubmed: 10386066
  2. Graffner-Nordberg M, Kolmodin K, Aqvist J, Queener SF, Hallberg A: Design, synthesis, computational prediction, and biological evaluation of ester soft drugs as inhibitors of dihydrofolate reductase from Pneumocystis carinii. J Med Chem. 2001 Jul 19;44(15):2391-402. Pubmed: 11448221
  3. Warlick CA, Diers MD, Wagner JE, McIvor RS: In vivo selection of antifolate-resistant transgenic hematopoietic stem cells in a murine bone marrow transplant model. J Pharmacol Exp Ther. 2002 Jan;300(1):50-6. Pubmed: 11752096
  4. Zhu WY, Bunni M, Priest DG, DiCapua JL, Dressler JM, Chen Z, Melera PW: Severe folate restriction results in depletion of and alteration in the composition of the intracellular folate pool, moderate sensitization to methotrexate and trimetrexate, upregulation of endogenous DHFR activity, and overexpression of metallothionein II and folate receptor alpha that, upon folate repletion, confer drug resistance to CHL cells. J Exp Ther Oncol. 2002 Sep-Oct;2(5):264-77. Pubmed: 12416030
  5. Sweeney CL, Frandsen JL, Verfaillie CM, McIvor RS: Trimetrexate inhibits progression of the murine 32Dp210 model of chronic myeloid leukemia in animals expressing drug-resistant dihydrofolate reductase. Cancer Res. 2003 Mar 15;63(6):1304-10. Pubmed: 12649191
  6. Polshakov VI, Birdsall B, Frenkiel TA, Gargaro AR, Feeney J: Structure and dynamics in solution of the complex of Lactobacillus casei dihydrofolate reductase with the new lipophilic antifolate drug trimetrexate. Protein Sci. 1999 Mar;8(3):467-81. Pubmed: 10091649
  7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352