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HCID 126941Erstellt: 27. Oktober 2026

Methotrexate

METHANOL-D4 · MTX · Trexall · Abitrexate · Methopterin · Methotrexat · sodium 4-[[4-[(2,4-diaminopteridin-6-yl)methyl-methyl-amino]benzoyl]am ino]-5-hydroxy-5-oxo-pentanoate · Rheumatrex

https://huagongshe.com/de/chemical/126941

Molekülstruktur von Methotrexate

Identifikatoren & physikalische Daten

CAS No.59-05-2
SummenformelC20H22N8O5
Durchschnittliche Molmasse454,4 g/mol
Monoisotopische Masse454,1713158 g/mol
SMILESCN(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc1
InChIKeyFBOZXECLQNJBKD-ZDUSSCGKSA-N
PubChem CID126941
ChEMBLCHEMBL34259
ChEBICHEBI:44185
EC No.200-413-8
DTXSIDDTXSID4020822
Lokaler NameMethotrexate

Chemische & physikalische Eigenschaften

XLogP-1,8
Polarare Oberfläche (TPSA)211
H-Brücken-Donoren5
H-Brücken-Akzeptoren12
Frei drehbare Bindungen9
Schwere Atome33
Formalladung0
Komplexität704
StoffklassenPharmaceutical
ArzneimittelPharmaceuticals -> Listed in ZINC15
LogP (Verteilungskoeffizient)log Kow = -1.85-2.2
Color/FormOrange-brown, crystalline powder
Löslichkeitless than 1 mg/mL at 66 °F (NTP, 1992)Insoluble in water , alcohol, chloroform, etherslightly soluble in dilute hydrochloric acidsoluble in dil solns of alkali hydroxides and carbonates.Practically insoluble in water and in alcohol.In water, 2.6X10+3 mg/L at 25 °C /Estimated/1.71e-01 g/LH2O: insolubleInsoluble. <0.1 g/100 mL at 19 ºC
Human DrugsBreast FeedingLactationMilk, HumanAbortifacient Agents, NonsteroidalAntimetabolites, AntineoplasticAntirheumatic AgentsFolic Acid AntagonistsImmunosuppressive AgentsFDA approved drugs -> Active ingredientEMA approved medicines: Human medicinePharmaceuticals
DecompositionWhen heated to decomposition it emits toxic fumes including /nitrogen oxides/.
Schmelzpunkt365 to 399 °F (decomposes) (NTP, 1992)Melting point: 185-204 °C. /Methotrexate monohydrate/195 °C356-399 °F195°C
Dampfdruck2.1X10-19 mm Hg at 25 °C /Estimated/
Optical RotationSpecific optical rotation: 20.4 + or - 0.6 deg at 21 °C/589 D (concentration by 0.1 N sodium hydroxide) maximum absorption: 243nm, A1= 388307 nm, A1 = 475 (in 0.1 n hydrogen chloride). 258 nm, A1= 544303 nm, A1= 546372 nm, A1= 177 (in 0.1 N sodium hydroxide)(c = 1, 0.05 M Na2CO3) [a]20 D = +17.0 - 19.5°
Henry-KonstanteHenry's Law constant = 1.5X10-31 atm-cu m/mol at 25 °C /Estimated/
Physical DescriptionMethotrexate is an odorless yellow to orange-brown crystalline powder. (NTP, 1992) It is a chemotherapy drug that interferes with DNA and RNA synthesis.SolidBright yellow-orange, odorless, crystalline powder.
Siedepunkt561.26°C (rough estimate)
Dichte1.4080 (rough estimate)
Brechungsindex1.6910 (estimate)
Flammpunkt11℃
LagerbedingungenKeep in dark place,Inert atmosphere,Store in freezer, under -20°C
Aggregatzustandpowder
pKa (Säurekonstante)pKa 3.04/4.99(H2O,t =25,I=0.0025) (Uncertain)
FarbeLight yellow to yellow
Biologische Quellesynthetic
Merck14,5985
BRN70669
BCS Class3
StabilitätStable, but light sensitive and hygroscopic. Incompatible with strong acids, strong oxidizing agents. Store at -15C or below.
Hauptanwendungenpharmaceutical (small molecule)
InChIKeyFBOZXECLQNJBKD-ZDUSSCGKSA-N
SMILESCN(Cc1cnc2nc(N)nc(N)c2n1)c3ccc(cc3)C(=O)N[C@@H](CCC(O)=O)C(O)=O
CAS Datenbank59-05-2(CAS DataBase Reference)
NIST chemische InformationenMethotrexate(59-05-2)
EPA chemische InformationenMethotrexate (59-05-2)

Sicherheit & Vorschriften

GHS-EinstufungDangerH301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]P203, P264, P264+P265, P270, P280, P301+P316, P302+P352, P305+P351+P338, P318, P321, P330, P332+P317, P337+P317, P362+P364, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 132 reports by companies from 16 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.
Regulatorische InformationenHazard Traits - Developmental ToxicityL-Glutamic acid, N-4-(2,4-diamino-6-pteridinyl)methylmethylaminobenzoyl-: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.
Weitere SicherheitsinformationenIMAP assessments - L-Glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-: Human health tier I assessment
DOT-KennzeichnungPoison
BrandgefahrenFlash point data for this chemical are not availablehowever, it is probably combustible. (NTP, 1992)
GesundheitsgefahrenSYMPTOMS: Symptoms of exposure to this compound include renal damage, leukopenia, headache, drowsiness, blurred vision, aphasia and hemiparesis. In addition, it causes developmental abnormalities of the craniofacial area and the musculoskeletal system, carcinogenic effects, leukemia, lymphoma effects including Hodgkin's disease, thrombocytopenia, bone marrow changes, other blood changes, cerebral spinal fluid effects, eye effects, blood pressure lowering, cough, dyspnea, fibrosis (pneumoconiosis), cyanosis, gastrointestinal effects, fatty liver degeneration and other liver changes, hepatitis, impaired liver function tests, skin tumors, fever, effects on inflammation or mediation of inflammation. Other symptoms include hemorrhagic enteritis, dermatitis, interstitial pneumonitis, neurotoxicity, nephrotoxicity, defective oogenesis o spermatogenesis, teratogenesis, hepatic dysfunction, progressive weight loss, depression, swelling and cytoplasmic vacuolization of the mucosal cells of the intestinal epithelium, desquamation of epithelial cells, extrusion of plasma into the lumen of the bowel, leukocytic infiltration of the submucosa, disturbance in the maturation of erythrocytes, rapid pathological alteration in myelopoiesis, diminution in content of lymphoid cells in lymphatic tissue and interference with embryogenesis. Interference with cellular reproduction, embryotoxicity, abortion, fetal defects, fertility impairment, menstrual dysfunction, hematopoiesis suppression, acute and chronic hepatotoxicity, nonspecific pneumonitis, chemical arachnoiditis manifested by headache, back pain and nuchal rigidity, paresis manifested by paraplegia, leukoencephalopathy manifested by confusion, irritability, somnolence, ataxia, dementia and convulsions, ulcerative stomatitis, nausea, alopecia, ecchymosis, telangiectasia, acne, furunculosis, vomiting, diarrhea, gastrointestinal ulceration and bleeding, azotemia, cystitis, hematuria, vaginal discharge, arthralgia, myalgia, metabolic changes, precipitating diabetes, osteoporotic effects, abdominal distress, malaise, undue fatigue, chills, dizziness, reduce resistance to infection, erythematous rash, pruritus, urticaria, gingivitis, photosensitivity, pigmentary changes, pharyngitis, anorexia, hematemesis, melena, transient oligospermia and sudden death may also result. In children it can cause pulmonary tract damage by ingestion, and blood dyscrasia intravenously. It may also cause lung changes, uro-genital toxicity and conjunctivitis. It may also cause septicemia and bleeding from various sites, mucositis, cerebral and cerebellar calcification, bone pain, fractures, aseptic necrosis of the head of the femur and shortness of breath. Granulocytopenia, hypoplasia of all elements of bone marrow and anemia may also occur. It may cause congenital malformation in the fetus and alter genetic material. Ulceration of the mouth, megaloblastic anemia, hypogammaglobulinemia, kidney damage, pulmonary reactions, progressive intellectual impairment, coma and pyrexia may also occur.

Anwendungen & Verwendung

History

Originally called amethopterin, methotrexate was discovered by the legendary American biochemist of Indian origin, Yella Pragada Subbarow, in collaboration with Sydney Farber from Children’s Hospital, Boston in the 1940s. By the 1970s, it was firmly established that MTX targets and saturates the binding sites of a key intracellular folate-dependent enzyme dihydrofolate reductase (DHFR) that is needed in large amounts to sustain the high proliferative activity of rapidly dividing cells, for example, cancer cells. A key finding of these researchers was that to be effective in killing the rapidly proliferative cancer cells, the high intracellular levels of MTX must be sustained to saturate >95% of the binding sites of the enzyme DHFR.

Verwenden

Methotrexate is used to treat severe lymphatic leukemia, choriocarcinoma, non-Hodgkin’s lymphoma, bone carcinoma, as well as head, neck, breast, and lung tumors.

FDA-AnforderungenThe Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl methotrexate sodium, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Methotrexate Sodium/
Reaktive GruppeAcids, Carboxylic
Special ReportsTung JP, Maibach HIPractical Use of Methotrexate in Psoriasis. Drugs 40: 697-712 (1990). A review of the use of methotrexate for the treatment of psoriasis is presented, including pathology, mechanism of action, pharmacokinetics, indications for use, pretreatment evaluations, monitoring parameters, dosage, overdose, drug interactions, adverse effects and the importance of patient information.
Reactivity ProfileMETHOTREXATE decomposes in very acidic or alkaline conditions. This chemical is incompatible with strong oxidizing agents and strong acids. (NTP, 1992)
Air and Water ReactionsThis chemical is sensitive to hydrolysis, oxidation and light. Insoluble in water.
Hazard Classes and CategoriesAcute Tox. 3 (100%)
BrandbekämpfungFires involving this material can be controlled using a dry chemical, carbon dioxide or Halon extinguisher. A water spray may also be used. (NTP, 1992)
Erste HilfeEYES: First check the victim for contact lenses and remove if present. Flush victim's eyes with water or normal saline solution for 20 to 30 minutes while simultaneously calling a hospital or poison control center. Do not put any ointments, oils, or medication in the victim's eyes without specific instructions from a physician. IMMEDIATELY transport the victim after flushing eyes to a hospital even if no symptoms (such as redness or irritation) develop.
LagerbedingungenMethotrexate sodium tablets should be protected from light and stored in well-closed containers at 15-30 °C. Methotrexate sodium injection and powder for injection should be protected from light and stored at 15-30 °C. /Methotrexate sodium/
Freisetung ohne BrandSMALL SPILLS AND LEAKAGE: If you spill this chemical, you should dampen the solid spill material with 5% ammonium hydroxide, then transfer the dampened material to a suitable container. Use absorbent paper dampened with 5% ammonium hydroxide to pick up any remaining material. Your contaminated clothing and the absorbent paper should be sealed in a vapor-tight plastic bag for eventual disposal. Wash all contaminated surfaces with 5% ammonium hydroxide followed by washing with a soap and water solution. Do not reenter the contaminated area until the Safety Officer (or other responsible person) has verified that the area has been properly cleaned.
EntsorgungsverfahrenSRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air qualitypotential migration in soil or watereffects on animal, aquatic, and plant lifeand conformance with environmental and public health regulations.
Isolation and EvacuationExcerpt from ERG Guide 151 [Substances - Toxic (Non-Combustible)]:
Personal Protective Equipment (PPE)RECOMMENDED RESPIRATOR: Where the neat test chemical is weighed and diluted, wear a NIOSH-approved half face respirator equipped with an organic vapor/acid gas cartridge (specific for organic vapors, HCl, acid gas and SO2) with a dust/mist filter. (NTP, 1992)
TreatmentAdminister charcoal as a slurry. Consider gastric lavage after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour). Protect airway by placement in Trendelenburg and left lateral decubitus position or by endotracheal intubation. Control any seizures first. Glucarpidase has been used intravenously in combination with thymidine and leucovorin to treat methotrexate toxicity. (T36)
WechselwirkungenOral neomycin may decreases absorption of oral methotrexate.Severe, sometimes fatal, toxicity (including hematologic and GI toxicity) has occurred following administration of a non-steroidal anti-inflammatory agent (eg, indomethacin, ketoprofen) concomitantly with methotrexate (particularly with high dose therapy) in patients with various malignant neoplasms, psoriasis, or rheumatoid arthritis.Concomitant use of penicillins (e.g., amoxicillin, carbenicillin, mezlocillin) may decrease renal clearance of methotrexate, presumably by inhibiting renal tubular secretion of the drug. Increased serum concentrations of methotrexate, resulting in GI or hematologic toxicity, have been reported in patients receiving low- or high-dose methotrexate therapy concomitantly with penicillins, and patients receiving the drugs concomitantly should be carefully monitored.Concurrent adminstration of intrathecal methotrexate and acyclovir may result in neurological abnormalitiesuse with caution.For more Interactions (Complete) data for METHOTREXATE (16 total), please visit the HSDB record page.
Gesundheitliche AuswirkungenA small percentage of patients develop hepatitis, and there is an increased risk of pulmonary fibrosis where dry cough can be an important sign. The higher doses of methotrexate often used in cancer chemotherapy can cause toxic effects to the rapidly-dividing cells of bone marrow and gastrointestinal mucosa. The resulting myelosuppression and mucositis are often prevented (termed Leucovorin "rescue"- as this is the folic acid based drug used) (L1079).
HepatotoxicityMethotrexate is well known to cause serum aminotransferase elevations and long term therapy has been linked to development of fatty liver disease, fibrosis and even cirrhosis. The literature on methotrexate is extensive, but with great variability in rates of liver test and biopsy abnormalities at different doses, dose regimens and durations of therapy.
UmweltverhaltenTERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a log Kow of -1.85(2) and a regression-derived equation(3), indicates that methotrexate is expected to have very high mobility in soil(SRC). The pKa of methotrexate is 4.70(4), indicating that this compound will primarily exist as an anion in the environment and anions do not volatilize and tend to have high mobility in soils. Methotrexate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.1X10-19 mm Hg(SRC), determined from a fragment constant method(5). Biodegradation may be an important fate process in the soil environment as indicated by a 95% biodegradation rate using the OECD Confirmatory test and a sewage inoculumhowever, the degradation product 7-hydroxymethotrexate is toxic and persistent(6).AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1(SRC), determined from a log Kow of -1.85(2) and a regression-derived equation(3), indicates that methotrexate is not expected to adsorb to suspended solids and sediment(SRC). The pKa of the carboxylic acid moiety of methotrexate is 4.70(4), indicating that this compound will primarily exist as an anion in the environment and anions do not volatilize(5). According to a classification scheme(6), an estimated BCF of 3.2(SRC), from its log Kow(2) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Methotrexate absorbs light at wavelengths >290 nm(8) and may be susceptible to photlysis in sunlit surface water but the rate of this reaction is not known. Biodegradation may be an important fate process in the aquatic environment as indicated by a 95% biodegradation rate using the OECD Confirmatory test and a sewage inoculumhowever, the degradation product 7-hydroxymethotrexate is toxic and persistent(9).ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), methotrexate, which has an estimated vapor pressure of 2.1X10-19 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase methotrexate may be removed from the air by wet and dry deposition(SRC). Methotrexate absorbs UV light at wavelengths >290 nm(3)therefore, methotrexate may be susceptible to photolysis however the rate of this reaction is not known(SRC).
Unerwünschte WirkungenEven a low dose of methotrexate is not free from adverse effects. The most common adverse effects are gastrointestinal (eg, nausea, vomiting, mucosal ulcers, and loss of appetite). These effects are noted in most patients and are easily managed. The most significant adverse effect of methotrexate is hepatotoxicity. These side effects are similar to folate deficiency and can be prevented by supplementing methotrexate with folic acid. A slightly elevated aminotransferase level is typical, but it is uncommon to have liver steatosis, fibrosis, and cirrhosis when taking a low dose of methotrexate. Over a long duration of treatment, ultrasound scanning and liver biopsy are required to ascertain the liver damage.
ExpositionspfadeInhalation (A314)dermal (A314)intravenous (A314) Oral absorption is dose dependent in adults and leukemic pediatric patients. In adults, peak serum levels are reached within one to two hours. At doses of 30 mg/m^2 or less, methotrexate is generally well absorbed with a mean bioavailability of 60%. At doses greater than 80 mg/m^2, the absorption of the doses is significantly less due to a saturation effect.
ToxizitätsübersichtSigns and Symptoms of OverdoseMethotrexate 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.
Signs and SymptomsSymptoms of overdose include bone marrow suppression and gastrointestinal toxicity.
Ongoing Test StatusThe following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=59-05-2]
Effluent ConcentrationsApproximately 1 ug/L methotrexate was reported in sewage effluentlocation specifics were not indicated(1).
Soil Adsorption/MobilityThe Koc of methotrexate is estimated as 1(SRC), using a log Kow of -1.85(1) and a regression-derived equation(2). According to a classification scheme(3), this estimated Koc value suggests that methotrexate is expected to have very high mobility in soil. The pKa of the carboxylic acid moiety of methotrexate is 4.70(4), indicating that this compound will primarily exist in anion form in the environment and anions generally do not adsorb more strongly to organic carbon and clay than their neutral counterparts(5). However, aromatic amines are expected to bind strongly to humus or organic matter in soils due to the high reactivity of the aromatic amino group(6,7), suggesting that mobility may be much lower in some soils(SRC).
F3-8-10
Wassergefährdungsklasse (WGK)3
TSCA-Inventar-StatusTSCA listed
UN-TransportnummerUN 2811 6.1/PG 3
Zollcode29335995
RTECS-Nr.MA1225000
R-Sätze (R)61-25-36/38-46-39/23/24/25-23/24/25-11
ToxizitätLD50 oral in rat: 135mg/kg
GefahrensymboleT,F
Sicherheitshinweise (S)53-26-36/37-45-36/37/39-36-16
Gefahrenklasse6.1(b)Acute Tox. 3 OralMuta. 2Repr. 1BSTOT RE 1
VerpackungsgruppeIII
Lagerklasse6.1C - Combustible acute toxic Cat.3toxic compounds or compounds which causing chronic effects
Gefahrstoffdaten59-05-2(Hazardous Substances Data)