生物活性

• 描述Ribonucleotide reductase (RNR) is an emzyme that catalyses the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis^[1]. RNR inhibitors are a family of anti-cancer drugs because they could affect the growth of tumor cells by interfering the DNA synthesis. Hydroxyurea (HU) is the inhibitor of ribonucleotide reductase (RNR) with IC50 value of 150 μM^[2].
  The ML L5178 cells, HU treatment at concentrations 0.25 mmol/l resulted in significant increases of DNA damage, detected as strand breaks in the alkaline comet assay ^[3]. After incubation with 2 mM HU for 4 hours on MCF7 cells, the level of phosphorylated RPA2 measured significantly increased and for 6 hours the percentage of cells with ssDNA was markedly decreased^[4].
  The pregnant C57BL/6 mice was intraperitoneally injected with 225 mg/kg HU and their embryos were explanted later. The RNR activity decreased significantly after 1 hour and the dNTP level in the brain tissues was attenuated with time^[5].
  
• 作用机制The HU is converted into its oxidized form compound III in the radical site of the ribonucleotide reductase protein. The compound III then reacts with the active site residues specially Tyr-176, and inhibits the radical generation and subsequently inhibits the RNR enzyme^[6].

• 动物研究
  剂量	Mice: 25 mg/kg - 100 mg/kg[7] (i.p.)
  给药途径	i.p.