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

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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/)
No information available.
Summary of Clinical Use Click here for help
Trimetrexate was originally approved by the US FDA in 1993, but use of this drug has since been discontinued. Trimetrexate was used in combination with folinic acid to treat moderate to severe Pneumocystis carinii pneumonia (PCP) in patients with compromised immune systems [3]. It was also used to treat some types of cancer including colon cancer [5] and investigated as a treatment for leiomyosarcoma [4] and methotrexate resistant skin lymphoma [2].
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Trimetrexate inhibits dihydrofolate reductase (DHFR) [6] across many species. Inhibition of this enzyme reduces active coenzyme tetrahydrofolate and folic acid supplies within cells (be they host cells or infection causing microbes). This leads to reduced thymidylate biosynthesis, and inhibition of folate-dependent formyltransferases. The net effect is disruption of DNA, RNA, and protein synthesis and this leads to cell death.