Methotrexate - CAS 59-05-2

Methotrexate - CAS 59-05-2 Catalog number: BADC-00037

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Methotrexate(WR19039; CL14377) can interfere with the growth of certain cells of the body, especially cells that reproduce quickly, such as cancer cells, bone marrow cells, and skin cells.

Category
ADCs Cytotoxin
Product Name
Methotrexate
CAS
59-05-2
Catalog Number
BADC-00037
Molecular Formula
C20H22N8O5
Molecular Weight
454.44
Methotrexate

Ordering Information

Catalog Number Size Price Quantity
BADC-00037 10 g $299
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Description
Methotrexate(WR19039; CL14377) can interfere with the growth of certain cells of the body, especially cells that reproduce quickly, such as cancer cells, bone marrow cells, and skin cells.
Synonyms
WR19039; CL14377; WR 19039; WR-19039; CL 14377; CL-14377
IUPAC Name
(2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
Canonical SMILES
CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
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
InChIKey
FBOZXECLQNJBKD-ZDUSSCGKSA-N
Density
1.5±0.1 g/cm3
Solubility
Soluble to 3900 mg/ml (8582 mm) in DMSO, not soluble in water
Melting Point
>188°C (dec.)
Flash Point
51.8 °F
Index Of Refraction
1.738
Optical Rotation
Specific optical rotation: 20.4 + or - 0.6 deg at 21 °C/589 D (concentration by 0.1 N sodium hydroxide) maximum absorption: 243nm, A1= 388;307 nm, A1 = 475 (in 0.1 n hydrogen chloride). 258 nm, A1= 544; 303 nm, A1= 546; 372 nm, A1= 177 (in 0.1 N sodium hydroxide);(c = 1, 0.05 M Na2CO3) [a]20 D = +17.0 - 19.5°
LogP
-0.24
PSA
210.54000
Vapour Pressure
2.1X10-19 mm Hg at 25 °C /Estimated/
UV Spectra
UV max (0.1N HCl) 244, 307 nm; UV max (0.1N NaOH) 257, 302, 370 nm;(0.1 N NaOH) max = 258 ± 2 nm E = 22,800 - 25,200;(0.1 N NaOH) max = 303 ± 2 nm E = 23,200 - 25,200;(0.1 N NaOH) max = 372 ± 2 nm E = 7,350 - 8,200
Mechanism Of Action
Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate. Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase. Inhibtion of nucleotide synthesis prevents cell division. In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate. This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.
Pharmacology
Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions. It has a long duration of action and is generally given to patients once weekly. Methotrexate has a narrow therapeutic index. Do not take methotrexate daily.
Toxicity (LD50)
The oral LD50 in rats is 135mg/kg and in mice is 146mg/kg. Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding. In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase.
In Vitro
The IC50 value of methotrexate against A549 cells was 23 nM for methotrexate. In a clonogenic assay against SCC25 human squamous cell carcinoma cells, the IC50 value of methotrexate was 27 nM.
In Vivo
Methotrexate (MTX) exposure reduces thymus and spleen indices of mice. Methotrexate markedly decreases white blood cells, thymic and splenic lymphocytes at dose ≥5 mg/kg. However, there is a significant difference between the treatment plus control group and the model group (p<0.01). The combination of grape seed proanthocyanidins and Siberian ginseng eleutherosides obviously diminishes the effects of Methotrexate exposure on indices of thymus and spleens in mice.
Clinical Trial Information
NCT NumberCondition Or DiseasePhaseStart DateSponsorStatus
NCT02011022Methotrexate Adverse ReactionNot Applicable2013-12-13The Children's Hospital of Zhejiang University School of MedicineCompleted
NCT04540250Methotrexate Adverse Reaction2020-09-07Beni-Suef UniversityCompleted
NCT00570817Methotrexate Induced NephrotoxicityNot Applicable2011-11-06University of AarhusCompleted
NCT00184886MethotrexateNot Applicable2006-02-14Radboud UniversityCompleted
NCT04483466Investigate the Effect(s) of Methotrexate Treatment on Arthritis Disease SeverityPhase 32021-07-06George Washington UniversityNot yet recruiting
Application
ADCs Cytotoxin
Appearance
Orange-brown, crystalline powder
Purity
>98%
Quantity
Milligrams-Grams
Shelf Life
≥360 days if stored properly
Shipping
Room temperature, or blue ice upon request.
Pictograms
Health Hazard; Acute Toxic
Signal Word
Danger
1. An algorithm to determine the mechanism of drug distribution in lipid-core nanocapsule formulations
Catiuscia P. Oliveira, Cristina G. Venturini, Adriana R. Pohlmann*. Soft Matter, 2013, 9, 1141–115
Indomethacin, diclofenac (acid) and indomethacin ethyl ester showed low solubility in water, with log D values higher than 2. The formulations were then prepared using drug concentrations higher than their saturation concentration in the aqueous phase. The log D value for indomethacin was similar to that determined for methotrexate ethyl ester, but IndOH-LNC1 and MTX(OEt)2-LNC0.5 were classified as having different types of distribution. On the other hand, the water solubilities of these drugs are slightly different (higher for methotrexate diethyl ester), while those of diclofenac (acid) and methotrexate diethyl ester are similar. Therefore, neither the log D nor the water solubility values can be used exclusively to explain the results. The difference between the distribution of methotrexate diethyl ester and those of indomethacin and diclofenac lies in the chemical nature of the functional groups, which are amines (ammonium) in the former and carboxylic (carboxylate) for the latter two cases. Thus, the results suggested that the drug interacts with PCL by hydrogen bonding, the O–H/O (indomethacin and diclofenac with PCL) interaction being stronger than N–H/O (methotrexate diethyl ester with PCL).
2. Gadolinium texaphyrin–methotrexate conjugates. Towards improved cancer chemotherapeutic agents
Wen-Hao Wei, Mark Fountain, Darren Magda*, Jonathan L. Sessler*. Org. Biomol. Chem. , 2005, 3 , 3290–3296
Therefore, in an effort to reduce non-tumor cell toxicity, chemotherapeutic agents better able to localize to tumors, either intrinsically or via attachment to tumor-directing carriers, are being developed. The latter species, often referred to as conjugates, show particular promise and have been shown to increase efficacy or decrease toxicity to non-tumor tissues in several cases. In this work we report the synthesis of conjugates of motexafin gadolinium, an experimental drug demonstrating significant tumor targeting, with methotrexate, a DNA synthesis inhibitor. The resulting conjugates, containing either ester or amide linkers, were tested in vitro for anti-proliferative activity using A549 lung cancer cells. Under conditions involving limited drug exposure times, the ester conjugate exhibited greater activity than the corresponding amide conjugate or methotrexate alone.
3. Direct measurement of drug–enzyme interactions by atomic force microscopy; dihydrofolate reductase and methotrexate
Shellie M. Rigby-Singleton, Stephanie Allen, Saul J. B. Tendler*. J. Chem. Soc., Perkin Trans. 2, 2002, 1722–1727
High-resolution crystal structures of the enzyme–inhibitor complex have also been elucidated. In particular, the inhibitor methotrexate (MTX) has been studied extensively over the last half century . Methotrexate upon binding to DHFR inhabits the same hydrophobic binding site as folate. Demonstrating a higher binding affinity for DHFR than folate, methotrexate acts as a competitive inhibitor of DHFR. When bound, methotrexate adopts an inverse orientation comparedto that of folate, but retains the same hydrogen bonding geometry as the enzyme–substrate complex. The binding site is configured of the αB helix connecting the αC helix (43–48,lc) to the βC sheet (58–62,lc), and a 9 to 23,lc residue loop (connecting the βA sheet and the αB helix).
4. Chromatic response of polydiacetylene vesicle induced by the permeation of methotrexate
Min Jae Shin, Ye Jin Kim and Jong-Duk Kim*. Soft Matter, 2015, 11, 5037—5043
In this study, a mixed vesicle of AEPCDA stabilized by vesicleforming surfactant, dimethyldioctadecylammonium chloride (DODAC) was fabricated as a model chromatic polydiacetylene layer, and methotrexate was used as a target material.We employed two types of detecting system in this study. One of the systems involved a simple detection of methotrexate on the exterior by the vesicle solution, whereas the other system involved detection of methotrexate inside the vesicle solution. In the second method, when methotrexate from the interior permeates out of the vesicle, the color of the vesicle can be changed. Fig. 1 shows a schematic color shift of the mixed vesicle during the permeation of methotrexate. This color shift of polydiacetylene layer can be used for the detection of the target material by both adsorption from the outside and permeation from the inside of the vesicle.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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