B. PYRIMIDINE ANALOGUES : 5-FLUOROURACIL, CAPECITABINE
5-FLUOROURACIL and CAPECITABINE decrease the biosynthesis of pyrimidine nucleotides by inhibiting thymidylate synthase, the enzyme that catalyzes the rate limiting step in DNA synthesis. This results in the “thymineless death” of rapidly growing cells. |
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Mechanisms of Action
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CAPECITABINE is converted to 5-FLUOROURACIL in cancer cells
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5-FU cannot be methylated by thymidylate synthase, causing sustained inhibition of the enzyme and decreased production of dTMP
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also can mimic function so that 5-FU is incorporated into DNA (via dUMP or dTMP) or RNA (via UTP), leading to other cytotoxic actions including DNA strand breakage and a decrease in protein synthesis
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LEUCOVORIN increases binding of 5-FU to thymidylate synthase thereby increasing 5-FU t1/2