Molecule Details
| InChIKey | FBOZXECLQNJBKD-ZDUSSCGKSA-N |
|---|---|
| Compound Name | Methotrexate |
| Canonical SMILES | CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1 |
| Clinical Status | Data-mined Candidate |
| Targets (Human+Pathogen) | 16 |
| Pfam Stratification | Cross-Family |
| Avg pChEMBL | 7.57 |
| Source | BindingDB;ChEMBL |
2D Structure
Activity Profile
DrugBank Annotations
| DrugBank ID | DB00563 |
|---|---|
| Drug Name | Methotrexate |
| CAS Number | 59-05-2 |
| Groups | approved investigational |
| ATC Codes | L04AX03 L01BA01 |
| Description | Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis.[A180322] This inhibition leads to suppression of inflammation as well as prevention of cell division.[A180322] Because of these effects, methotrexate is often used to treat inflammation caused by ... |
Categories: Abortifacient Agents Abortifacient Agents, Nonsteroidal Agents Causing Muscle Toxicity Antimetabolites Antineoplastic Agents Antineoplastic and Immunomodulating Agents Antirheumatic Agents BCRP/ABCG2 Substrates Biological Factors Cancer immunotherapy Cardiotoxic antineoplastic agents Cytochrome P-450 CYP3A Substrates Cytochrome P-450 CYP3A4 Substrates Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index Cytochrome P-450 Substrates Cytotoxins Dermatologicals Drugs causing inadvertant photosensitivity Drugs that are Mainly Renally Excreted Enzyme Inhibitors Folic Acid Analogues Folic Acid Antagonists Hepatotoxic Agents Heterocyclic Compounds, Fused-Ring Immunologic Factors Immunosuppressive Agents Immunotherapy Myelosuppressive Agents Narrow Therapeutic Index Drugs Nephrotoxic agents Noxae Nucleic Acid Synthesis Inhibitors OAT1/SLC22A6 inhibitors OAT3/SLC22A8 Inhibitors OAT3/SLC22A8 Substrates OAT3/SLC22A8 Substrates with a Narrow Therapeutic Index OATP1B1/SLCO1B1 Substrates OATP1B3 substrates P-glycoprotein substrates P-glycoprotein substrates with a Narrow Therapeutic Index Photosensitizing Agents Pigments, Biological Pteridines Pterins Reproductive Control Agents Toxic Actions
Cross-references: BindingDB: 66082 ChEBI: 44185 CHEMBL34259 ChemSpider: 112728 Drugs Product Database (DPD): 5900 C01937 D00142 PDB: MTX PharmGKB: PA450428 PubChem:126941 PubChem:46507678 RxCUI: 6851 Therapeutic Targets Database: DNC000933 Wikipedia: Methotrexate ZINC: ZINC000001529323
Target Activities (16)
| Target | Gene | Organism | Category | Pfam | pChEMBL | Type | Source |
|---|---|---|---|---|---|---|---|
| P00374 | DHFR | Homo sapiens | Human | PF00186 | 8.0 | IC50 | ChEMBL;BindingDB |
| P22102 | GART | Homo sapiens | Human | PF00586 PF02769 PF00551 PF01071 PF02843 PF02844 | 8.0 | IC50 | ChEMBL |
| P41440 | SLC19A1 | Homo sapiens | Human | PF01770 | 7.9 | IC50 | ChEMBL;BindingDB |
| P04818 | TYMS | Homo sapiens | Human | PF00303 | 7.1 | IC50 | ChEMBL;BindingDB |
| P09429 | HMGB1 | Homo sapiens | Human | PF00505 PF09011 | 7.0 | Kd | ChEMBL;BindingDB |
| Q96NT5 | SLC46A1 | Homo sapiens | Human | PF07690 | 6.9 | IC50 | ChEMBL;BindingDB |
| P14207 | FOLR2 | Homo sapiens | Human | PF03024 | 6.8 | IC50 | ChEMBL;BindingDB |
| P15328 | FOLR1 | Homo sapiens | Human | PF03024 | 6.8 | IC50 | ChEMBL;BindingDB |
| Q9Y6Q9 | NCOA3 | Homo sapiens | Human | PF23172 PF07469 PF16279 PF16665 PF08815 PF00989 PF14598 PF08832 | 6.7 | IC50 | ChEMBL |
| P31939 | ATIC | Homo sapiens | Human | PF01808 PF02142 | 6.1 | Ki | ChEMBL;BindingDB |
| P07382 | Leishmania major | Pathogen | PF00186 PF00303 | 9.3 | IC50 | ChEMBL;BindingDB | |
| P00380 | folA | Enterococcus faecium | Pathogen | PF00186 | 8.8 | IC50 | ChEMBL |
| P00469 | thyA | Lacticaseibacillus casei | Pathogen | PF00303 | 8.6 | IC50 | BindingDB |
| B0BL08 | dfrA17 | Escherichia coli | Pathogen | PF00186 | 8.2 | IC50 | BindingDB |
| Q81R22 | dfrA | Bacillus anthracis | Pathogen | PF00186 | 7.8 | IC50 | ChEMBL;BindingDB |
| Q01782 | PTR1 | Leishmania major | Pathogen | PF00106 PF13561 | 7.1 | Ki | ChEMBL;BindingDB |
DrugBank Target Actions (48)
| Target | Gene | Target Name | Action | Type |
|---|---|---|---|---|
| P02768 | ALB | Albumin | binder | carriers |
| P31939 | ATIC | Bifunctional purine biosynthesis protein ATIC | inhibitor | enzymes |
| P52209 | PGD | 6-phosphogluconate dehydrogenase, decarboxylating | inhibitor | enzymes |
| P00374 | DHFR | Dihydrofolate reductase | substrate | enzymes |
| P04818 | TYMS | Thymidylate synthase | substrate | enzymes |
| P06621 | P06621 | Carboxypeptidase G2 | substrate | enzymes |
| P08684 | CYP3A4 | Cytochrome P450 3A4 | substrate | enzymes |
| P42898 | P42898 | Methylenetetrahydrofolate reductase (NADPH) | substrate | enzymes |
| Q05932 | FPGS | Folylpolyglutamate synthase, mitochondrial | substrate | enzymes |
| Q06278 | AOX1 | Aldehyde oxidase | substrate | enzymes |
| Q92820 | Q92820 | Gamma-glutamyl hydrolase | substrate | enzymes |
| P00374 | DHFR | Dihydrofolate reductase | inhibitor | targets |
| P04818 | TYMS | Thymidylate synthase | inhibitor | targets |
| P31939 | ATIC | Bifunctional purine biosynthesis protein ATIC | inhibitor | targets |
| P41440 | SLC19A1 | Reduced folate transporter | modulator | targets |
| Q96NT5 | SLC46A1 | Proton-coupled folate transporter | modulator | targets |
| Q6ZQN7 | SLCO4C1 | Solute carrier organic anion transporter family member 4C1 | binder | transporters |
| O15438 | ABCC3 | ATP-binding cassette sub-family C member 3 | inhibitor | transporters |
| O15439 | O15439 | ATP-binding cassette sub-family C member 4 | inhibitor | transporters |
| P33527 | ABCC1 | Multidrug resistance-associated protein 1 | inhibitor | transporters |
| Q4U2R8 | SLC22A6 | Solute carrier family 22 member 6 | inhibitor | transporters |
| Q5T3U5 | Q5T3U5 | ATP-binding cassette sub-family C member 10 | inhibitor | transporters |
| Q8TCC7 | SLC22A8 | Organic anion transporter 3 | inhibitor | transporters |
| Q92887 | ABCC2 | ATP-binding cassette sub-family C member 2 | inhibitor | transporters |
| Q96NT5 | SLC46A1 | Proton-coupled folate transporter | inhibitor | transporters |
| O15438 | ABCC3 | ATP-binding cassette sub-family C member 3 | substrate | transporters |
| O15439 | O15439 | ATP-binding cassette sub-family C member 4 | substrate | transporters |
| P08183 | ABCB1 | ATP-dependent translocase ABCB1 | substrate | transporters |
| P14207 | FOLR2 | Folate receptor beta | substrate | transporters |
| P15328 | FOLR1 | Folate receptor alpha | substrate | transporters |
| P33527 | ABCC1 | Multidrug resistance-associated protein 1 | substrate | transporters |
| P41440 | SLC19A1 | Reduced folate transporter | substrate | transporters |
| P46059 | SLC15A1 | Solute carrier family 15 member 1 | substrate | transporters |
| P46721 | P46721 | Solute carrier organic anion transporter family member 1A2 | substrate | transporters |
| P53985 | SLC16A1 | Monocarboxylate transporter 1 | substrate | transporters |
| Q4U2R8 | SLC22A6 | Solute carrier family 22 member 6 | substrate | transporters |
| Q7Z2H8 | Q7Z2H8 | Proton-coupled amino acid transporter 1 | substrate | transporters |
| Q8TCC7 | SLC22A8 | Organic anion transporter 3 | substrate | transporters |
| Q92887 | ABCC2 | ATP-binding cassette sub-family C member 2 | substrate | transporters |
| Q96J66 | Q96J66 | ATP-binding cassette sub-family C member 11 | substrate | transporters |
| Q96NT5 | SLC46A1 | Proton-coupled folate transporter | substrate | transporters |
| Q9NPD5 | SLCO1B3 | Solute carrier organic anion transporter family member 1B3 | substrate | transporters |
| Q9NSA0 | SLC22A11 | Solute carrier family 22 member 11 | substrate | transporters |
| Q9NYB5 | Q9NYB5 | Solute carrier organic anion transporter family member 1C1 | substrate | transporters |
| Q9UIG8 | Q9UIG8 | Solute carrier organic anion transporter family member 3A1 | substrate | transporters |
| Q9UNQ0 | ABCG2 | Broad substrate specificity ATP-binding cassette transporter ABCG2 | substrate | transporters |
| Q9Y694 | Q9Y694 | Solute carrier family 22 member 7 | substrate | transporters |
| Q9Y6L6 | SLCO1B1 | Solute carrier organic anion transporter family member 1B1 | substrate | transporters |