A-771726

A-771726 is an active metabolite of the prodrug leflunomide (Item No. 14860) that inhibits dihydroorotate dehydrogenase (DHODH; IC₅₀ = 0.23 µM).¹ A-771726 inhibits the production of prostaglandin E₂ (PGE₂; Item No. 14010) in TNF-α- or IL-1α-stimulated isolated human synoviocytes (IC₅₀s = 7 and 3 μM, respectively).² It inhibits the proliferation of isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations of 25 and 100 µM.³ A-771726 (3 and 10 mg/kg) delays disease onset and decreases neurological deficits in a rat model of experimental autoimmune encephalomyelitis (EAE) induced by complete Freund’s adjuvant (CFA) and M. tuberculosis.⁴ Formulations containing teriflunomide have been used in the treatment of multiple sclerosis.

WARNING This product is not for human or veterinary use.

1. Papageorgiou, C., Zurini, M., Weber, H.-P., et al. Leflunomide’s bioactive metabolite has the minimal structural requirements for the efficient inhibition of human dihydroorotate dehydrogenase. Bioorg. Chem. 25(4), 233-238 (1997).

2. Burger, D., Begué-Pastor, N., Benavent, S., et al. The active metabolite of leflunomide, A77 1726, inhibits the production of prostaglandin E₂, matrix metalloproteinase 1 and interleukin 6 in human fibroblast-like synoviocytes. Rheumatology (Oxford) 42(1), 89-96 (2003).

3. Li, L., Liu, J., Delohery, T., et al. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J. Neuroimmunol. 265(1-2), 82-90 (2013).

4. Merrill, J.E., Hanak, S., Pu, S.-F., et al. Teriflunomide reduces behavioral, electrophysiological, and histopathological deficits in the Dark Agouti rat model of experimental autoimmune encephalomyelitis. J. Neurol. 256(1), 89-103 (2009).