Biochemicals & reagents
1) Manna et al. (1999), Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression; J. Immunol., 162 2095 2) Davis et al. (1996), The immunosuppressive metabolite of leflunomide is a potent inhibitor of human dihydroorotate dehydrogenase; Biochemistry, 35 1270 3) Seah et al. (2008), Oxidative bioactivation and toxicity of leflunomide in immortalized human hepatocytes and kinetics of the non-enzymatic conversion to its major metabolite, A77 1726; Drug Metab. Lett., 2 153
A77 1726 is a pyrimidine biosynthesis inhibitor and immunomodulator (1) which inhibits the mitochondrial dihydroorotate dehydrogenase (DHODH) (2). Leflunomide is rapidly metabolized in human hepatocytes to A77 1726 (3) and is also cell permeable.