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Record Information
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2018-05-20 20:16:54 UTC
Secondary Accession Numbers
  • HMDB15288
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]
Trimetrexic acidGenerator
Monohydrate, monoacetate trimetrexateMeSH
Trimetrexate ipsen brandMeSH
Trimetrexate monohydrate, monoacetateMeSH
Hydrate, trimetrexateMeSH
Ipsen brand OF trimetrexateMeSH
Trimetrexate hydrateMeSH
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
InChI Identifier
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as quinazolinamines. These are heterocyclic aromatic compounds containing a quianazoline moiety substituted by one or more amine groups.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
Sub ClassBenzodiazines
Direct ParentQuinazolinamines
Alternative Parents
  • Quinazolinamine
  • Methoxyaniline
  • Aminophenyl ether
  • Aniline or substituted anilines
  • Phenylalkylamine
  • Phenoxy compound
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Secondary aliphatic/aromatic amine
  • Alkyl aryl ether
  • Aralkylamine
  • Aminopyrimidine
  • Pyrimidine
  • Benzenoid
  • Imidolactam
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Ether
  • Azacycle
  • Secondary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Amine
  • Primary amine
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Physiological effect

Health effect:


Route of exposure:

Biological location:


Industrial application:

Physical Properties
Experimental Properties
Melting Point215 - 217 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.031 g/LNot Available
LogP2Not Available
Predicted Properties
Water Solubility0.031 g/LALOGPS
pKa (Strongest Acidic)17.04ChemAxon
pKa (Strongest Basic)7.54ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area117.54 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity107.7 m³·mol⁻¹ChemAxon
Polarizability40.24 ųChemAxon
Number of Rings3ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0ugj-0409000000-97a2080cda5a33464953View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dr-0409000000-a9fcda741827d39a85bcView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0903000000-d3e9f90709b809eb4f3dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-2911000000-97342eb0d2ab1fad8f13View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0209000000-e610f7928dd8d57d924cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-0209000000-c28a10a57fcb7298832aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00kf-9431000000-249d2de16520a2966585View in MoNA
Biological Properties
Cellular Locations
  • Membrane (predicted from logP)
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Normal Concentrations
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01157 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01157 details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiospecimenValueOriginal ageOriginal sexOriginal conditionComments
Blood0.000 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0.000 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01157
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID5381
KEGG Compound IDC11154
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTrimetrexate
METLIN IDNot Available
PubChem Compound5583
PDB IDNot Available
ChEBI ID119101
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available


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:
Uniprot ID:
Molecular weight:
  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 ]