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].
• 细胞研究
• Cell Data

  Cell Lines	Concentration	Assay Type	Time	Activity Description	Data Sources
  HL-60	-	Growth Inhibition Assay	72 h	IC50=8.601 μg/mL	24095176
  HT-29	-	Growth Inhibition Assay	72 h	IC50> 25 μg/mL	24095176
  MCF-7	-	Growth Inhibition Assay	72 h	IC50=20 μg/mL	24095176

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• 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

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02817113	Head and Neck Neoplasms	Phase 1	Unknown	December 2017	Taiwan ... more >> National Taiwan University Hospital Not yet recruiting Taipei, Taiwan, 100 Contact: Ruey-Long Hong, MD PhD          Taipei Veterans General Hospital Recruiting Taipei, Taiwan, 112 Contact: Muh-Hwa Yang, MD PhD          Chang Gung Memorial Hospital, Linkou Branch Recruiting Taoyuan, Taiwan, 333 Contact: Hung-Ming Wang, MD PhD Collapse <<
  NCT02270606	Mucinous Adenocarcinoma of the... more >> Rectum Recurrent Rectal Cancer Signet Ring Adenocarcinoma of the Rectum Rectal Adenocarcinoma Stage IIA Rectal Cancer Stage IIB Rectal Cancer Stage IIC Rectal Cancer Stage IIIA Rectal Cancer Stage IIIB Rectal Cancer Stage IIIC Rectal Cancer Collapse <<	Phase 1	Active, not recruiting	May 14, 2023	United States, Virginia ... more >> Virginia Commonwealth University/Massey Cancer Center Richmond, Virginia, United States, 23219 Collapse <<
  NCT02289378	Docetaxel, Oxaliplatin and Flu... more >>orouracil Collapse <<	Phase 2	Unknown	October 2017	China, Guangdong ... more >> The Sixth Affiliated Hospital of Sun Yat-sen University Recruiting Guangzhou, Guangdong, China, 510655 Contact: Jian Xiao, Ph D    86-2038250745    xiao_jian@139.com    Principal Investigator: Ping Lan, Ph D Collapse <<

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• 参考文献

• [1] Longley DB, Harkin DP, et al. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8.

  [2] Diasio RB, Harris BE, et al. Clinical pharmacology of 5-fluorouracil. Clin Pharmacokinet. 1989 Apr;16(4):215-37.

  [3] Santi DV, McHenry CS, et al. Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate. Biochemistry. 1974 Jan 29;13(3):471-81.

  [4] Glazer RI, Lloyd LS, et al. Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture. Mol Pharmacol. 1982 Mar;21(2):468-73.

  [5] Cao Z, Zhang Z, et al. Antitumor and immunomodulatory effects of low-dose 5-FU on hepatoma 22 tumor-bearing mice. Oncol Lett. 2014 Apr;7(4):1260-1264. Epub 2014 Feb 6.

  [6] Song MK, Park MY, et al. 5-Fluorouracil-induced changes of intestinal integrity biomarkers in BALB/c mice. J Cancer Prev. 2013 Dec;18(4):322-9.

  [7] Li J, Chen Y, et al. Simultaneous determination of the novel anti-tumor candidate drug MDH-7 and 5-fluorouracil in rat plasma by LC-MS/MS: Application to pharmacokinetic interactions. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Sep 15;1095:235-240.

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