trimetrexate   Click here for help

GtoPdb Ligand ID: 7613

Synonyms: CI-898 | Neutrexin® | trimetrexate glucuronate
Approved drug
trimetrexate is an approved drug (FDA (1993))
Compound class: Synthetic organic
Comment: Trimetrexate is a quinazoline derivative dihydrofolate reductase inhibitor [6]. Chemically it is a methotrexate (MTX) analogue.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

trimetrexate is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 5
Hydrogen bond donors 3
Rotatable bonds 6
Topological polar surface area 117.54
Molecular weight 369.18
XLogP 2.18
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COc1cc(NCc2ccc3c(c2C)c(N)nc(n3)N)cc(c1OC)OC
Isomeric SMILES COc1cc(NCc2ccc3c(c2C)c(N)nc(n3)N)cc(c1OC)OC
InChI 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 Key NOYPYLRCIDNJJB-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Rosowsky A, Mota CE, Queener SF, Waltham M, Ercikan-Abali E, Bertino JR. (1995)
2,4-Diamino-5-substituted-quinazolines as inhibitors of a human dihydrofolate reductase with a site-directed mutation at position 22 and of the dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii.
J Med Chem, 38 (5): 745-52. [PMID:7877140]
2. Sarris AH, Phan A, Duvic M, Romaguera J, McLaughlin P, Mesina O, King K, Medeiros LJ, Rassidakis GZ, Samuels B et al.. (2002)
Trimetrexate in relapsed T-cell lymphoma with skin involvement.
J Clin Oncol, 20 (12): 2876-80. [PMID:12065565]
3. Sattler FR, Allegra CJ, Verdegem TD, Akil B, Tuazon CU, Hughlett C, Ogata-Arakaki D, Feinberg J, Shelhamer J, Lane HC et al.. (1990)
Trimetrexate-leucovorin dosage evaluation study for treatment of Pneumocystis carinii pneumonia.
J Infect Dis, 161 (1): 91-6. [PMID:2136905]
4. Smith HO, Blessing JA, Vaccarello L. (2002)
Trimetrexate in the treatment of recurrent or advanced leiomyosarcoma of the uterus: a phase II study of the Gynecologic Oncology Group.
Gynecol Oncol, 84 (1): 140-4. [PMID:11748990]
5. Stewart JA, McCormack JJ, Tong W, Low JB, Roberts JD, Blow A, Whitfield LR, Haugh LD, Grove WR, Lopez AJ et al.. (1988)
Phase I clinical and pharmacokinetic study of trimetrexate using a daily x5 schedule.
Cancer Res, 48 (17): 5029-35. [PMID:2970294]
6. Wong BK, Woolf TF, Chang T, Whitfield LR. (1990)
Metabolic disposition of trimetrexate, a nonclassical dihydrofolate reductase inhibitor, in rat and dog.
Drug Metab Dispos, 18 (6): 980-6. [PMID:1981548]