Teriflunomide (A 77-1726) is the principal active metabolite of leflunomide, an approved therapy for rheumatoid arthritis and multiple sclerosis.

Teriflunomide primarily acts as an inhibitor of dihydroorotate dehydrogenase (DHODH), a key mitochondrial enzyme involved in the de novo synthesis of pyrimidines in rapidly proliferating cells. By reducing the activity of high-avidity proliferating T lymphocytes and B lymphocytes, teriflunomide likely attenuates the inflammatory response to autoantigens in MS. Notably, DHODH blockade does not affect resting or homeostatically proliferating hematopoietic cell lines, as pyrimidine pools in these cells can be generated through an alternate 'salvage pathway,' which is independent of DHODH. Thus, teriflunomide can be considered a cytostatic rather than a cytotoxic drug to leukocytes [1].