5-fluorouracil and dihydropyrimidine dehydrogenase.
Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme of (fluorinated) pyrimidine degradation that plays a significant role in the pharmacokinetics of 5-fluorouracil (5-FU). In addition, a catabolite of 5-FU induces a certain toxicity, and the sensitivity of 5-FU is determined by DPD activity in tumors. DPD is thus important clinically. Drugs have been developed that control variations of the pharmacokinetics of 5-FU by controlling or inhibiting DPD, thereby reducing toxicity and improving sensitivity. These fluorinated pyrimidines with DPD-inhibiting activity, called DPD-inhibitory fluoropyrimidines, contribute to oral therapy with 5-FU for cancer. This paper summarizes the important role of DPD in cancer chemotherapy with 5-FU.
Kubota
Tetsuro
T
Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. tkubota@sc.itc.keio.ac.jp
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010088:Oxidoreductases / Q000378:metabolism / Q000494:pharmacology*; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship
D000964:Antimetabolites, Antineoplastic; D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil