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Leflunomide-d4 is intended for use as an internal standard for the quantification of leflunomide by GC- or LC-MS. Leflunomide is a synthetic isoxazol and a prodrug form of A-771726 , a dihydroorotate dehydrogenase inhibitor.1 Leflunomide inhibits de novo pyrimidine synthesis to regulate T lymphocyte progression through the cell cycle. It inhibits proliferation and activation of T cells when used at concentrations of 25 and 100 µM, respectively, for naÏve and memory CD4+ T cells.2 It also reduces the production of Th1 effector cells and increases differentiation of Th2 cells in vitro and in splenocytes isolated from KLH-immunized mice. Leflunomide (35 mg/kg per day) reduces and prevents inflammation in a proteoglycan-induced mouse model of rheumatoid arthritis.3 Formulations containing leflunomide have been used in the treatment of active rheumatoid arthritis.

1.Breedveld, F.C., and Dayer, J.-M.Leflunomide: Mode of action in the treatment of rheumatoid arthritisAnn. Rheum. Dis.59(11)841-849(2000) 2.Dimitrova, P., Skapenko, A., Herrmann, M.L., et al.Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes Th2 cell differentiationJ. Immunol.169(6)3392-3399(2002) 3.Glant, T.T., Mikecz, K., Bartlett, R.R., et al.Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomideImmunopharmacology23(2)105-116(1992)

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