Leflunomide

Leflunomide (original brand name Arava) is an immunosuppressive disease-modifying antirheumatic drug (DMARD), used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Product information

CAS Number: 75706-12-6

Molecular Weight: 270.21

Formula: C12H9F3N2O2

Synonym:

Arava

Leflunomidum

HWA-486

Chemical Name: 5-methyl-N-[4-(trifluoromethyl)phenyl]-1, 2-oxazole-4-carboxamide

Smiles: CC1ON=CC=1C(=O)NC1C=CC(=CC=1)C(F)(F)F

InChiKey: VHOGYURTWQBHIL-UHFFFAOYSA-N

InChi: InChI=1S/C12H9F3N2O2/c1-7-10(6-16-19-7)11(18)17-9-4-2-8(3-5-9)12(13,14)15/h2-6H,1H3,(H,17,18)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO 54 mg/mL (199.84 mM) Ethanol 54 mg/mL (199.84 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

In Vivo:

Leflunomide is able to prevent and reverse allograft and xenograft rejection in rodents, dogs, and monkeys.

References:

1. Fox RI, et al. Clin Immunol, 1999, 93(3), 198-208.
2. Xu X, et al. J Biol Chem. 1995, 270(21), 12398-12403.
3. Davis JP, et al. Biochemistry, 1996, 35(4), 1270-1273.

Products are for research use only. Not for human use.