Anti-neoplastic/cancer drugs

Question 1

What enzyme does 5-fluorouracil inhibit? In which pathway?

Answer 1

-5-FU inhibits thymidylate synthase –> decrease in production of dTMP (which becomes thymine in de novo pyrimidine synthesis)

Question 2

What enzyme does methotrexate inhibit in humans? What drugs act like methotrexate but in bacteria or protozoa?

Answer 2

• methotrexate (MTX) inhibits dihydrofolate reductase (which reduces dTMP production)
• trimethoprim (TMP) in bacteria
• pyrimethamine in protozoa

Question 3

What drug(s) inhibit de novo purine synthesis? (FDA-approved for ALL; used also for AML, CML, Non-Hodgkin’s lymphoma, IBD)

Answer 3

6-mercaptopurine and its prodrug azathioprine both inhibit de novo purine synthesis

Question 4

Which drug inhibits ribonucleotide reductase? (UDP –> dUDP in pyrimidine de novo synthesis) Used in CML and sickle cell crisis

Answer 4

hydroxyurea

Question 5

What anti-transplant rejection drug inhibits IMP dehydrogenase (which converts IMP to GMP in purine synthesis)? Which drug has the same mechanism but is used for Hep. C and RSV?

Answer 5

• mycophenolate is the anti-transplant rejection drug

- ribavirin is the anti-viral drug