5-Fluorouracil is a potent antitumor agent that affects pyrimidine synthesis by inhibiting thymidylate synthetase thus depleting intracellular dTTP pools.
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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].
5-Fluorouracil 细胞研究
细胞系
浓度
检测类型
检测时间
活动说明
数据源
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
NCI-H292
Growth Inhibition Assay
72 h
IC50> 25 μg/mL
24095176
5-Fluorouracil 动物研究
Dose
Mice (i.p.): min = 10 mg/kg[5], max = 200 mg/kg[6]
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