| Compound Information | SONAR Target prediction |
| Name: | METHOTREXATE(+/-) |
| Unique Identifier: | SPE01500398 |
| MolClass: | Checkout models in ver1.5 and ver1.0 |
| Molecular Formula: | |
| Molecular Weight: | 432.265 g/mol |
| X log p: | 6.466 (online calculus) |
| Lipinksi Failures | 2 |
| TPSA | 103.89 |
| Hydrogen Bond Donor Count: | 0 |
| Hydrogen Bond Acceptors Count: | 13 |
| Rotatable Bond Count: | 10 |
| Canonical Smiles: | CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(cc1)C(=O)NC(CCC(O)=O)C(O)=O |
| Source: | synthetic |
| Therapeutics: | antineoplastic, antirheumatic, folic acid antagonist |
| Generic_name: | Methotrexate |
| Chemical_iupac_name: | (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid |
| Drug_type: | Approved Drug |
| Pharmgkb_id: | PA450428 |
| Kegg_compound_id: | C01937 |
| Drugbank_id: | APRD00353 |
| Melting_point: | 195 oC |
| H2o_solubility: | 2600 mg/L |
| Logp: | -1.08 |
| Isoelectric_point: | 4.7 |
| Cas_registry_number: | 05/02/1959 |
| Mass_spectrum: | http://webbook.nist.gov/cgi/cbook.cgi?Spec=C59052&Index=0&Type=Mass&Large=on |
| Drug_category: | Antirheumatic Agents; Immunosuppressive Agents; Dermatologic Agents; Antimetabolites; Abortifacient Agents; Antineoplastic Agents; ATC:L01BA01; ATC:L04AX03 |
| Indication: | For the treatment of gestational choriocarcinoma, chorioadenoma destruens and hydatidiform mole. Also for the treatment of severe psoriasis and severe, active, classical or definite rheumatoid arthritis. |
| Pharmacology: | Methotrexate is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Methotrexate inhibits folic acid reductase which is responsible for the conversion of folic acid to tetrahydrofolic acid. At two stages in the biosynthesis of purines and at one stage in the synthesis of pyrimidines, one-carbon transfer reactions occur which require specific coenzymes synthesized in the cell from tetrahydrofolic acid. Tetrahydrofolic acid itself is synthesized in the cell from folic acid with the help of an enzyme, folic acid reductase. Methotrexate looks a lot like folic acid to the enzyme, so it binds to it quite strongly and inhibits the enzyme. Thus, DNA synthesis cannot proceed because the coenzymes needed for one-carbon transfer reactions are not produced from tetrahydrofolic acid because there is no tetrahydrofolic acid. Methotrexate selectively affects the most rapidly dividing cells (neoplastic and psoriatic cells). Methotrexate is also indicated in the management of severe, active, classical, or definite rheumatoid arthritis. |
| Mechanism_of_action: | Methotrexate anti-tumor activity is a result of the inhibition of folic acid reductase, leading to inhibition of DNA synthesis and inhibition of cellular replication. The mechanism involved in its activity against rheumatoid arthritis is not known. |
| Organisms_affected: | Humans and other mammals |
| Found: 59 active | as graph: single | with analogs | 1 2 3 4 5 6 7 8 9 10 Next >> [59] |
| Species: | 4932 |
| Condition: | BCK1 |
| Replicates: | 2 |
| Raw OD Value: r im | 0.1365±0.00494975 |
| Normalized OD Score: sc h | 0.1516±0.0016248 |
| Z-Score: | -29.0347±2.57942 |
| p-Value: | 0 |
| Z-Factor: | 0.920174 |
| Fitness Defect: | INF |
| Bioactivity Statement: | Toxic |
| ps |
| DBLink | Rows returned: 9 | 1 2 Next >> |
| 4112 | 2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid |
| 23893 | disodium 2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioate |
| 61796 | sodium 4-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]-5-hydroxy-5-oxo-pentanoate |
| 72440 | (2R)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid |
| 126941 | (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid |
| 165528 | (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]amino]pentanedioic acid hydrate |
| internal high similarity DBLink | Rows returned: 4 |
| LOPAC 00621 | 0.9848 |
| SPE01500679 | 0.9848 |
| LOPAC 00676 | 1.0000 |
| LOPAC 00699 | 1.0000 |
| active | Cluster 1716 | Additional Members: 9 | Rows returned: 0 |
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