METHOTREXATE

Search structure
Trade Names:
Synonyms:
Status: Approved (1953)
Entry Type: Small molecule
Molecule Category: Parent
ATC: L01BA01
UNII: YL5FZ2Y5U1

Structure
InChI Key FBOZXECLQNJBKD-ZDUSSCGKSA-N
Smile CN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
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

Physicochemical Descriptors

Property Name Value
Molecular Formula C20H22N8O5
Molecular Weight 454.45
AlogP 0.27
Hydrogen Bond Acceptor 10.0
Hydrogen Bond Donor 5.0
Number of Rotational Bond 9.0
Polar Surface Area 210.54
Molecular species ACID
Aromatic Rings 3.0
Heavy Atoms 33.0

Experimental and Estimated Properties

Property Name Value Unit Method
log P (octanol-water) -1.85E+00 - EXP
pKa Dissociation Constant 4.7 - EXP
Henry's Law Constant 1.54E-31 atm-m3/mole EST
Atmospheric OH Rate Constant 3.17E-10 cm3/molecule-sec EST
Water Solubility 2600 mg/L EST
Vapor Pressure 2.09E-19 mm Hg EST

Pharmacology

Action Mechanism of Action Reference
INHIBITOR Dihydrofolate reductase inhibitor DailyMed
Primary Target
dihydrofolate reductase
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Enzyme Ligase
- 10 - - -
Enzyme Oxidoreductase
- 1-1500 0-1700 0-3900 0-91
Enzyme Transferase
- 40000-100000 - 45000 0
Enzyme
- 1-1500 0-1700 0-3900 0-91
Membrane receptor
- 106-211 - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC19 family of vitamin transporters
- 12-12 - 3500 60
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC21/SLCO family of organic anion transporting polypeptides
- - - -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC22 family of organic cation and anion transporters
- - - - 26
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC46 family of folate transporters
- 121-121 - - -
Unclassified protein
- - 24-500 - -

Metabolites

visNetwork

Indications

Mesh Heading Maximum Phase Mesh ID Reference
Breast Neoplasms 4 D001943 ClinicalTrials
Neoplasms 4 D009369 ClinicalTrials
Precursor Cell Lymphoblastic Leukemia-Lymphoma 4 D054198 ClinicalTrials
Mycosis Fungoides 4 D009182 ClinicalTrials
Precursor Cell Lymphoblastic Leukemia-Lymphoma 4 D054198 ClinicalTrials
Neoplasms 4 D009369 ClinicalTrials
Arthritis 4 D001168 ClinicalTrials
Choriocarcinoma 4 D002822 ClinicalTrials
Psoriasis 4 D011565 ClinicalTrials
Lymphoma, Non-Hodgkin 4 D008228 ClinicalTrials
Breast Neoplasms 4 D001943 ClinicalTrials
Urinary Bladder Neoplasms 3 D001749 ClinicalTrials
Leukemia, Myelogenous, Chronic, BCR-ABL Positive 3 D015464 ClinicalTrials
Dermatomyositis 3 D003882 ClinicalTrials
Dermatomyositis 3 D003882 ClinicalTrials
Sarcoma 3 D012509 ClinicalTrials
Carcinoma, Squamous Cell 3 D002294 ClinicalTrials
Uveitis, Intermediate 3 D015867 ClinicalTrials
Carcinoma, Squamous Cell 3 D002294 ClinicalTrials
Arthritis, Psoriatic 3 D015535 ClinicalTrials
Cardiovascular Diseases 3 D002318 ClinicalTrials
Osteoarthritis 3 D010003 ClinicalTrials
Asthma 3 D001249 ClinicalTrials
Hydatidiform Mole 3 D006828 ClinicalTrials
Head and Neck Neoplasms 3 D006258 ClinicalTrials
Dermatitis, Atopic 3 D003876 ClinicalTrials
Osteosarcoma 3 D012516 ClinicalTrials
Lymphoma 3 D008223 ClinicalTrials
Leukemia, Myeloid, Acute 3 D015470 ClinicalTrials
Alopecia Areata 3 D000506 ClinicalTrials
Lymphoma, Large B-Cell, Diffuse 3 D016403 ClinicalTrials
Uveitis 3 D014605 ClinicalTrials
Leukemia 3 D007938 ClinicalTrials
Leukemia, Biphenotypic, Acute 3 D015456 ClinicalTrials
Lymphoma, Follicular 3 D008224 ClinicalTrials
Hodgkin Disease 3 D006689 ClinicalTrials
Myelodysplastic Syndromes 3 D009190 ClinicalTrials
Leukemia, Biphenotypic, Acute 3 D015456 ClinicalTrials
Leukemia, Promyelocytic, Acute 3 D015473 ClinicalTrials
Lupus Erythematosus, Systemic 3 D008180 ClinicalTrials
Medulloblastoma 3 D008527 ClinicalTrials
Lymphoma, Large-Cell, Anaplastic 3 D017728 ClinicalTrials
Brain Neoplasms 3 D001932 ClinicalTrials
Multiple Sclerosis 3 D009103 ClinicalTrials
Spondylitis, Ankylosing 3 D013167 ClinicalTrials
Myeloproliferative Disorders 3 D009196 ClinicalTrials
Graft vs Host Disease 3 D006086 ClinicalTrials
Neuroectodermal Tumors, Primitive 3 D018242 ClinicalTrials
Granulomatosis with Polyangiitis 3 D014890 ClinicalTrials
Head and Neck Neoplasms 3 D006258 ClinicalTrials
Pemphigoid, Bullous 3 D010391 ClinicalTrials
Hearing Loss, Sensorineural 3 D006319 ClinicalTrials
Giant Cell Arteritis 3 D013700 ClinicalTrials
Liver Cirrhosis, Biliary 3 D008105 ClinicalTrials
Leukemia, Myelomonocytic, Chronic 3 D015477 ClinicalTrials
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 3 D054218 ClinicalTrials
Gestational Trophoblastic Disease 3 D031901 ClinicalTrials
Vasculitis 3 D014657 ClinicalTrials
Pregnancy, Ectopic 3 D011271 ClinicalTrials
Sarcoidosis 3 D012507 ClinicalTrials
Leukemia, Erythroblastic, Acute 3 D004915 ClinicalTrials
Leukemia, Monocytic, Acute 3 D007948 ClinicalTrials
Leukemia, Myelomonocytic, Acute 3 D015479 ClinicalTrials
Myeloproliferative Disorders 3 D009196 ClinicalTrials
Leukemia, Megakaryoblastic, Acute 3 D007947 ClinicalTrials
Leukemia, Myeloid, Acute 3 D015470 ClinicalTrials
Anemia, Refractory 3 D000753 ClinicalTrials
Anemia, Refractory, with Excess of Blasts 3 D000754 ClinicalTrials
Vitiligo 3 D014820 ClinicalTrials
Central Nervous System Neoplasms 3 D016543 ClinicalTrials
Crohn Disease 3 D003424 ClinicalTrials
Urinary Bladder Neoplasms 3 D001749 ClinicalTrials
Brain Neoplasms 3 D001932 ClinicalTrials
Head and Neck Neoplasms 3 D006258 ClinicalTrials
Uterine Cervical Neoplasms 3 D002583 ClinicalTrials
Macular Edema 3 D008269 ClinicalTrials
Urethral Neoplasms 3 D014523 ClinicalTrials
Graft vs Host Disease 3 D006086 ClinicalTrials
Choroid Plexus Neoplasms 3 D016545 ClinicalTrials
Lymphoma, Follicular 3 D008224 ClinicalTrials
Leukemia, Biphenotypic, Acute 3 D015456 ClinicalTrials
Granuloma, Lethal Midline 3 D006103 ClinicalTrials
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 3 D054218 ClinicalTrials
Urinary Bladder Neoplasms 3 D001749 ClinicalTrials
Vitreoretinopathy, Proliferative 3 D018630 ClinicalTrials
Retroperitoneal Fibrosis 3 D012185 ClinicalTrials
Osteosarcoma 3 D012516 ClinicalTrials
Colorectal Neoplasms 2 D015179 ClinicalTrials
Neurofibromatosis 1 2 D009456 ClinicalTrials
Immunoblastic Lymphadenopathy 2 D007119 ClinicalTrials
Polycythemia Vera 2 D011087 ClinicalTrials
Ependymoma 2 D004806 ClinicalTrials
Waldenstrom Macroglobulinemia 2 D008258 ClinicalTrials
Neoplasm Metastasis 2 D009362 ClinicalTrials
Sezary Syndrome 2 D012751 ClinicalTrials
Leukemia, Hairy Cell 2 D007943 ClinicalTrials
Severe Combined Immunodeficiency 2 D016511 ClinicalTrials
Hemoglobinuria, Paroxysmal 2 D006457 ClinicalTrials
Leukemia, Lymphocytic, Chronic, B-Cell 2 D015451 ClinicalTrials
Wiskott-Aldrich Syndrome 2 D014923 ClinicalTrials
Ovarian Neoplasms 2 D010051 ClinicalTrials
Urticaria 2 D014581 ClinicalTrials
Lymphohistiocytosis, Hemophagocytic 2 D051359 ClinicalTrials
Neuroblastoma 2 D009447 ClinicalTrials
Myocardial Infarction 2 D009203 ClinicalTrials
Mesothelioma 2 D008654 ClinicalTrials
Ovarian Neoplasms 2 D010051 ClinicalTrials
Multiple Myeloma 2 D009101 ClinicalTrials
Hematologic Neoplasms 2 D019337 ClinicalTrials
Primary Myelofibrosis 2 D055728 ClinicalTrials
Fibromatosis, Aggressive 2 D018222 ClinicalTrials
Myasthenia Gravis 2 D009157 ClinicalTrials
Leukemia, Large Granular Lymphocytic 2 D054066 ClinicalTrials
Leukemia-Lymphoma, Adult T-Cell 2 D015459 ClinicalTrials
Myelodysplastic-Myeloproliferative Diseases 2 D054437 ClinicalTrials
Central Serous Chorioretinopathy 2 D056833 ClinicalTrials
Leukemia, Lymphoid 2 D007945 ClinicalTrials
Blast Crisis 2 D001752 ClinicalTrials
Hematologic Neoplasms 2 D019337 ClinicalTrials
Colorectal Neoplasms 2 D015179 ClinicalTrials
Schizophrenia 2 D012559 ClinicalTrials
Constriction, Pathologic 2 D003251 ClinicalTrials
Burkitt Lymphoma 2 D002051 ClinicalTrials
Lymphoma, T-Cell, Peripheral 2 D016411 ClinicalTrials
Leukemia, Myelomonocytic, Juvenile 2 D054429 ClinicalTrials
Histiocytosis, Langerhans-Cell 2 D006646 ClinicalTrials
Primary Myelofibrosis 2 D055728 ClinicalTrials
Lymphoma, AIDS-Related 2 D016483 ClinicalTrials
Lymphoma, Mantle-Cell 2 D020522 ClinicalTrials
Carcinoma, Merkel Cell 2 D015266 ClinicalTrials
Shwachman-Diamond Syndrome 2 D000081003 ClinicalTrials
Kidney Neoplasms 2 D007680 ClinicalTrials
Coronary Disease 2 D003327 ClinicalTrials
Mesothelioma 2 D008654 ClinicalTrials
Anemia, Aplastic 2 D000741 ClinicalTrials
Anemia, Sickle Cell 2 D000755 ClinicalTrials
Osteopetrosis 2 D010022 ClinicalTrials
Colitis, Ulcerative 2 D003093 ClinicalTrials
Severe Acute Respiratory Syndrome 1 D045169 ClinicalTrials
Melanoma 1 D008545 ClinicalTrials
Inflammation 1 D007249 ClinicalTrials
Fanconi Anemia 1 D005199 ClinicalTrials
Leukemia, Plasma Cell 1 D007952 ClinicalTrials
HIV Infections 1 D015658 ClinicalTrials
Scleroderma, Systemic 1 D012595 ClinicalTrials
Malaria 1 D008288 ClinicalTrials

Related Entries

MCS

Scaffolds

Salt

Side Effects from Label

Side effects Relative Frequency (%) Labels
Immune system disorders Anaphylactic shock 1.0

Adverse Reactions

SOC By Demographic Distribution
System Organ Classification (SOC)
Relative Frequency (%)
General disorders and administration site conditions
12.8
Injury, poisoning and procedural complications
12.18
Skin and subcutaneous tissue disorders
6.99
Gastrointestinal disorders
6.65
Nervous system disorders
6.45
Infections and infestations
5.94
Musculoskeletal and connective tissue disorders
5.54
Vascular disorders
5.47
Respiratory, thoracic and mediastinal disorders
4.96
Product issues
4.09
Investigations
3.68
Blood and lymphatic system disorders
3.16
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
2.98
Cardiac disorders
2.9
Surgical and medical procedures
2.35
Immune system disorders
2.2
Psychiatric disorders
2.05

Cross References

Resources Reference
CAS NUMBER 59-05-2
ChEBI 44185
ChEMBL CHEMBL34259
DrugBank DB00563
DrugCentral 1751
EPA CompTox DTXSID4020822
FDA SRS YL5FZ2Y5U1
Human Metabolome Database HMDB0014703
Guide to Pharmacology 4674
KEGG C01937
PDB MTX
PharmGKB PA450428
PubChem 126941
SureChEMBL SCHEMBL3711
ZINC ZINC000001529323
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