Teriflunomide selectively and reversibly inhibits dihydro-orotate
dehydrogenase, an enzyme in the de novo synthesis pathway of pyrimidines, resulting in reduced proliferation of peripheral T- and B-lymphocytes, and hence reduced numbers of lymphocytes crossing the blood-brain barrier and causing CNS damage.
Teriflunomide reduces B- and T-cell proliferation by reversibly inhibiting the mitochondrial enzyme dihydro-orotate
dehydrogenase (Warnke et al., 2009).
The metabolite is a reversible inhibitor of the mitochondrial enzyme dihydro-orotate
dehydrogenase (DHODH) that exerts anti-inflammatory, antiproliferative, and immunosuppressive effects, but the mechanisms by which it does so are not yet completely understood.
Its ability to inhibit dihydro-orotate
dehydrogenase (DHODH), a key cellular enzyme involved in de novo pyrimidine synthesis appears to dominate its therapeutic effect.