product name Leflunomide
Description: Leflunomide (also known as HWA486) is a pyrimidine synthesis inhibitor belonging to the DMARD, used as an immunosuppressant agent. Leflunomide is used as an immunosuppressive disease-modifying antirheumatic drug (DMARD) for the treatment of active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.
References: Biochemistry. 1996 Jan 30;35(4):1270-3; J Biol Chem. 1995 May 26;270(21):12398-403.
270.21
Formula
C12H9F3N2O2
CAS No.
75706-12-6
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 54 mg/mL (199.8 mM)
Water: <1 mg/mL
Ethanol: 54 mg/mL (199.8 mM)
Solubility (In vivo)
Synonyms
HWA486
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19409888
| In Vitro |
In vitro activity: Leflunomide is actually a prodrug that is processed in vivo to the active metabolite A771726，which has been shown to inhibit proliferation of mononuclear and T-cells. Leflunomide is an inhibitor of several protein tyrosine kinases, with IC50 values between 30 mM and 100 mM in vitro cellular and enzymatic assays. Leflunomide is capable of inhibiting anti-CD3- and interleukin-2 (IL-2)-stimulated T cell proliferation. Leflunomide is able to inhibit p59fyn and p56lck activity in in vitro tyrosine kinase assays. Leflunomide also inhibits Ca2+ mobilization in Jurkat cells stimulated by anti-CD3 antibody but not in those stimulated by ionomycin. Leflunomide also inhibits distal events of anti-CD3 monoclonal antibody stimulation, namely, IL-2 production and IL-2 receptor expression on human T lymphocytes. Leflunomide also inhibits tyrosine phosphorylation in CTLL-4 cells stimulated by IL-2. Leflunomide is an immunomodulatory drug that may exert its effects by inhibiting the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH), which plays a key role in the de novo synthesis of the pyrimidine ribonucleotide uridine monophosphate (rUMP). Leflunomide prevents the expansion of activated and autoimmune lymphocytes by interfering with the cell cycle progression due to inadequate production of rUMP and utilizing mechanisms involving p53. Kinase Assay: Cell Assay: |
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| In Vivo | Leflunomide is able to prevent and reverse allograft and xenograft rejection in rodents, dogs, and monkeys. |
| Animal model | |
| Formulation & Dosage | |
| References | Biochemistry. 1996 Jan 30;35(4):1270-3; J Biol Chem. 1995 May 26;270(21):12398-403. |
