Which proliferation signal inhibitor inhibits dihydroorotate dehydrogenase?

• A. Mycophenolate
• B. Sirolimus
• C. Leflunomide
• D. Everolimus

Answer: (C)

Leflunomide blocks the enzyme dihydroorotate dehydrogenase, a key step in de novo pyrimidine synthesis. By inhibiting this mitochondrial enzyme, lymphocytes can’t efficiently produce pyrimidine nucleotides needed for DNA replication, so activated T and B cells cannot proliferate as they normally would. This direct interruption of pyrimidine synthesis is what makes it the proliferation signal inhibitor that targets DHODH.

Other agents in this group act on different parts of cell growth pathways. Mycophenolate mofetil inhibits IMP dehydrogenase, reducing purine nucleotide synthesis, which also dampens lymphocyte proliferation but not through DHODH. Sirolimus and everolimus inhibit mTOR signaling, blocking growth and division downstream of IL-2 receptors rather than the pyrimidine synthesis pathway.