ATC Group: L04AK Dihydroorotate dehydrogenase (DHODH) inhibitors

Leflunomide is a disease-modifying anti-rheumatic agent with antiproliferative properties. A771726, the active metabolite of leflunomide, inhibits the human enzyme dihydroorotate dehydrogenase (DHODH) and exhibits antiproliferative activity.

Teriflunomide is an immunomodulatory agent with anti-inflammatory properties that selectively and reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHO-DH), which functionally connects with the respiratory chain. As a consequence of the inhibition, teriflunomide generally reduces the proliferation of rapidly dividing cells that depend on de novo synthesis of pyrimidine to expand. The exact mechanism by which teriflunomide exerts its therapeutic effect in MS is not fully understood, but this is mediated by a reduced number of lymphocytes.