methotrexate   

GtoPdb Ligand ID: 4815

Synonyms: Abitrexate® | amethopterin | Nordimet® | Rasuvo®
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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2D Structure
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Physico-chemical Properties
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
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
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
dihydrofolate reductase 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.