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Hydroxyurea

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Chemical Structure| 127-07-1 同义名 : N-(氨基羰基)羟胺 ;Hydroxycarbamide;NCI C04831;Droxia;Carbamoyl oxime;Biosupressin;NSC 32065
CAS号 : 127-07-1
货号 : A145474
分子式 : CH4N2O2
纯度 : 98%+
分子量 : 76.055
MDL号 : MFCD00007943
存储条件：

粉末 Keep in dark place,Inert atmosphere,Room temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(657.42 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 50 mg/mL(657.42 mM)，配合低频超声助溶
动物实验配方：
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].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
L1210 Leukemia cells Growth inhibition assay Concentration required for 50% inhibition of cell growth (L1210 Leukemia), IC50=21.3796 μM 2991520
P388 leukemic cell Proliferation assay 24-48 h Antiproliferative activity of compound expressed as concentration that inhibits 50% of growth of P388 leukemic cell suspension from 24 to 48 hr after compound addition, IC50=32 μM 2709372
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

13.15mL

2.63mL

1.31mL

65.75mL

13.15mL

6.57mL

131.49mL

26.30mL

13.15mL
参考文献

[1]Elledge SJ, Zhou Z, et al. Ribonucleotide reductase: regulation, regulation, regulation. Trends Biochem Sci. 1992;17(3):119-23.

[2]Tholander F, Sjöberg BM. Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format. Proc Natl Acad Sci U S A. 2012;109(25):9798-803.

[3]Osterman Golkar S, Czene S, et al. Intracellular deoxyribonucleotide pool imbalance and DNA damage in cells treated with hydroxyurea, an inhibitor of ribonucleotide reductase. Mutagenesis. 2013;28(6):653-60.

[4]Shi W, Feng Z, et al. The role of RPA2 phosphorylation in homologous recombination in response to replication arrest. Carcinogenesis. 2010;31(6):994-1002.

[5]Guan Z, Wang X, et al. dNTP deficiency induced by HU via inhibiting ribonucleotide reductase affects neural tube development. Toxicology. 2015.

[6]Iman M, Khansefid Z, et al. Modeling and Proposed Molecular Mechanism of Hydroxyurea Through Docking and Molecular Dynamic Simulation to Curtail the Action of Ribonucleotide Reductase. Recent Pat Anticancer Drug Discov. 2016;11(4):461-468.