MOA of leflunomide

MOA of leflunomide

Leflunomide is metabolized by the liver to its active metabolite, teriflunomide (A771726), which inhibits dihydroorotate dehydrogenase leading to a decrease in de novo synthesis of uridine, resulting in a decrease in the synthesis of pyrimidines. Activated but not resting lymphocytes (B cells > T cells) have low pools of pyrimidine nucleotides, making them sensitive to this drug. When uridine is lowered below a critical level, the tumor suppressor p53 is activated, arresting lymphocyte cell division in the G1 stage of the cell cycle.

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