2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid hydrate

• ChemBase ID: 134377
• Molecular Formular: C20H24N8O6
• Molecular Mass: 472.45456
• Monoisotopic Mass: 472.18188053
• SMILES: CN(Cc1cnc2c(n1)c(nc(n2)N)N)c1ccc(cc1)C(=O)NC(CCC(=O)O)C(=O)O.O
• Canonical SMILES: OC(=O)CCC(C(=O)O)NC(=O)c1ccc(cc1)N(Cc1cnc2c(n1)c(N)nc(n2)N)C.O
• InChI: InChI=1S/C20H22N8O5.H2O/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);1H2
• InChIKey: FPJYMUQSRFJSEW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[(4-{[(2,4-diaminopteridin-6-yl)methyl](methyl)amino}phenyl)formamido]pentanedioic acid hydrate
• IUPAC Traditional name: hydrate methotrexate
• Synonyms: DL-4-Amino-N10-methylpteroylglutamic acid; MTX; (±)Amethopterin hydrate; 氨甲叶酸; 氨甲喋呤

Database IDs

• CAS Number: 60388-53-6(anhydrous)
• EC Number: 262-213-7
• MDL Number: MFCD00150845
• PubChem SID: 162228653; 24891167
• PubChem CID: 24207740

CALCULATED PROPERTIES

• Acid pKa: 3.2608879
• H Acceptors: 12
• H Donor: 5
• LogD (pH = 5.5): -3.640823
• LogD (pH = 7.4): -6.5636883
• Log P: -0.23654379
• Molar Refractivity: 119.2108 cm^3
• Polarizability: 43.521362 Å^3
• Polar Surface Area: 210.54 Å^2
• Rotatable Bonds: 9
• Lipinski's Rule of Five: false

PROPERTIES

Physical Property

• Solubility: H2O: insoluble; NaOH: soluble (minimal amount of 0.1 N NaOH to solubilize, then dilute in neutral buffer or saline)
• Apperance: yellow to yellow with an orange cast powder

Safety Information

• RTECS: MA1224100
• European Hazard Symbols: Toxic (T)
• UN Number: 1544
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 2
• Risk Statements: 61-25-36/38
• Safety Statements: 53-26-36/37-45
• GHS Pictograms: GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H315-H319-H360
• GHS Precautionary statements: P201-P301 + P310-P305 + P351 + P338-P308 + P313
• Personal Protective Equipment: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 1544 6.1/PG 2
• Storage Temperature: -20°C

Pharmacology Properties

• Gene Information: human ... DHFRP1(573971), FPGS(2356), SLC19A1(6573), TYMS(7298)mouse ... Dhfr(13361)rat ... Dhfr(24312)

Product Information

• Purity: ≥95%

DETAILS

Sigma Aldrich - A7019

包装
25 mg in poly bottle
500 mg in glass bottle
Reconstitution
Add a minimal amount of 0.1 N NaOH to solubilize, then dilute in neutral buffer or saline. Diluted stock is stable for 1 week refrigerated and for 1 month frozen at -20 °C. References: Cell & Tissue Culture: Laboratory Procedures, Chapter 27, Page 27D:3.2 (A. Doyle, et al., eds, John Wiley) and Cell Biology: A Laboratory Handbook, vol. 2, page 417 (Julio E. Celis, ed., Academic Press).
Application
Amethopterin is a folic acid antagonist and potent anticancer agent. Amethopterin blocks DNA synthesis by preventing the production of tetrahydrofolate cofactors which are required to make thymidine. Amethopterin is actively transported into cells by the folate transporter where it is converted to a high molecular weight polyglutamate metabolite by folylpolyglutamate synthase, a dihydrofolate reductase inhibitor.
Biochem/physiol Actions
Amethopterin is a folic acid antagonist and potent anticancer agent. Blocks DNA synthesis by blocking the production of tetrahydrofolate covactors required for the synthesis of thymidine. Amethopterin is actively transported into cells by the folate transporter. In the cell, it is converted to a high molecular weight polyglutamate metabolite by folylpolyglutamate synthase that, in turn, binds to dihydrofolate reductase and inhibits its activity. Amethopterin-polyglutamate is degraded intracellularly by γ-glutamyl hydrolase.