product name Methotrexate
Description: Methotrexate (also known as NCI-C04671) is an antimetabolite and antifolate drug, which acts by inhibiting the metabolism of folic acid in activated peripheral T cells. Methotrexate is used as an antineoplastic and immunosuppressant. Methotrexate binds to and inhibits the enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate synthesis and, subsequently, inhibition of DNA and RNA syntheses.
References: J Clin Invest. 1998 Jul 15;102(2):322-8; J Clin Invest. 1993 Dec;92(6):2675-82.
454.44
Formula
C20H22N8O5
CAS No.
59-05-2
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 90 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
2% DMSO+30% PEG 300+5% Tween 80+ddH2O: 5 mg/mL
Synonyms
NCI-C04671
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19410546
| In Vitro |
In vitro activity: Methotrexate (0.1-10 mM) induces apoptosis of in vitro activated T cells from human peripheral blood. Methotrexate achieves clonal deletion of activated T cells in mixed lymphocyte reactions. Methotrexate can selectively delete activated peripheral blood T cells by a CD95-independent pathway. Methotrexate is taken up by cells via the reduced folate carrier and then is converted within the cells to polyglutamates. Methotrexate leads to diminished production of leukotriene B4 by neutrophils stimulated ex vivo. Methotrexate polyglutamates inhibit the enzyme aminoimidazolecarboxamidoadenosineribonucleotide (AICAR) transformylase more potently than the other enzymes involved in purine biosynthesis. Methotrexate is also known to suppress TNF activity by suppressing TNF-induced nuclear factor-κB activation in vitro, in part related to a reduction in the degradation and inactivation of an inhibitor of this factor, IκBα, and probably related to the release of adenosine. Methotrexate suppresses the production of both TNF and IFN-γ by T-cell-receptor-primed T lymphocytes from both healthy human donors and RA patients. Methotrexate treatment is associated with a significant decrease of TNF-α-positive CD4+ T cells, while the number of T cells expressing the anti-inflammatory cytokine IL-10 increased. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | Methotrexate increases splenocyte AICAR content, raised adenosine concentrations in exudates from carrageenan-inflamed air pouches, and markedly inhibits leukocyte accumulation in inflamed air pouches in mice. Methotrexate-mediated reduction in leukocyte accumulation is partially reversed by injection of adenosine deaminase (ADA) into the air pouch, completely reverses by a specific adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX), but not affected by an adenosine A1 receptor antagonist, 8-cyclopentyl-dipropylxanthine in mice. |
| Animal model | |
| Formulation & Dosage | |
| References | J Clin Invest. 1998 Jul 15;102(2):322-8; J Clin Invest. 1993 Dec;92(6):2675-82. |
