methotrexate   Click here for help

GtoPdb Ligand ID: 4815

Synonyms: Abitrexate® | amethopterin | Nordimet® | Rasuvo®
Approved drug PDB Ligand Immunopharmacology Ligand
methotrexate is an approved drug (FDA (1953), EMA (2016))
Compound class: Synthetic organic
Comment: Methotrexate is a folate (folic acid) analogue that is classified as an antimetabolite and antifolate drug, and a disease-modifying anti-rheumatic drug (DMARD). It is used clinically for its antiproliferative and anti-inflammatory effects. The primary action of methotrexate is inhibition of the enzyme dihydrofolate reductase (DHFR). DHFR is essential for the production of precursors that are required for de novo purine synthesis.
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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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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 CDK toolkit. 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 13
Hydrogen bond donors 5
Rotatable bonds 10
Topological polar surface area 210.54
Molecular weight 454.17
XLogP -2.67
No. Lipinski's rules broken 1
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.

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Canonical SMILES OC(=O)CCC(C(=O)O)NC(=O)c1ccc(cc1)N(Cc1cnc2c(n1)c(N)nc(n2)N)C
Isomeric 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
InChI Key FBOZXECLQNJBKD-ZDUSSCGKSA-N
Transporters Moving this Compound Across a Lipid Membrane
Transporter EC number Reaction Reference
Reduced folate transporter 1
Proton-coupled folate transporter 5
Selectivity at enzymes
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
dihydrofolate reductase Primary target of this compound Hs Inhibitor Inhibition 8.9 pKi - 8
⤷ pKi 8.9 (Ki 1.2x10-9 M) [8]
Selectivity at transporters
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
Reduced folate transporter 1 Hs Inhibitor Inhibition 5.3 pKi - 7
⤷ pKi 5.3 (Ki 4.7x10-6 M) [7]
Description: Inhibition of [3H]methotrexate uptake by CCRF-CEM (human T lymphoblast) cells.
Selectivity at other protein targets
Key to terms and symbols Click column headers to sort
Target Sp. Type Action Value Parameter Concentration range (M) Reference
high mobility group box 1 Hs Inhibitor Inhibition 7.6 pKd - 9
⤷ pKd 7.6 (Kd 2.4x10-8 M) [9]
Description: Binding affinity to N-terminal 6His-tagged HMGB1 by SPR assay