生物活性

• 描述5-Fluorouracil (5-FU), or combined with other chemotherapeutic agents, is widely used in the treatment of a range of cancers, including colorectal and breast cancers, head and neck cancers, cancers of the aerodigestive tract^[1]. 5-Fluorouracil can disrupt RNA synthesis through RNA mis-incorporation by its active metabolites, as well as block dTMP synthesis through inhibition of thymidylate synthase. After entering into cells, 5-Fluorouracil can be converted to its active metabolites, fluorodeoxyuridine monophosphate (FdUMP), fluorodeoxyuridine triphosphate (FdUTP) and fluorouridine triphosphate^[2]. FdUMP can inhibit the thymidylate synthase through binding to the nucleotide-binding site of thymidylate synthase, thus blocking the binding of normal substrate dUMP and inhibiting dTMP synthesis. And this will cause the disruption of DNA replication and repair^[3]. FUTP can extensively incorporate into RNA and disrupt RNA processing and function^[4]. Thus, 5-Fluorouracil showed cytotoxicity in various cells.
• 作用机制The mechanism of cytotoxicity of 5-FU has been ascribed to the mis-incorporation of fluoronucleotides into RNA and DNA, as well as the inhibition of thymidylate synthase^[4].

• 动物研究
  剂量	Mice (i.p.): min = 10 mg/kg[5], max = 200 mg/kg[6]
  给药途径	i.p.
  动物药代数据	Animal Rats[7] Dose 10 mg/kg Administration i.v. T1/2 0.28 ± 0.04 h MRT0→∞ 0.26 ± 0.01 h AUC0→∞ 3198.47 ± 429.12 ng/ml·h AUC0→t 3187.85 ± 427.28 ng/ml·h CL 3.16 ± 0.40 L/h/kg MRT0→t 0.25 ± 0.01 h C0 9289.63 ± 1089.57 ng/ml