放射增敏剂IPdR的作用机制及研究进展

目的:对放射增敏剂5-碘-2-嘧啶酮-2’脱氧核糖(IPdR)进行综述,为放射增敏剂提供研发思路及参考。方法:通过查阅国内外相关文献,分析IPdR理化性质、作用机理及其作为放射增敏剂的优势,总结IPdR的药效和毒理学研究结果以及Ⅰ期临床的最新进展,对Ⅱ期临床试验的开展及安全评估方案进行展望。结果与结论:IPdR作为IUdR(5-碘-2’去氧尿苷)的前体化合物,是一种卤代核苷类似物,可通过口服进入人体。血液中的IPdR在醛氧化酶的作用下,逐渐转化为能够发挥药效的IUdR,进而与肿瘤细胞的DNA结合,提高了病灶组织的放射敏感性,从而发挥药效。根据前期药效和毒理学数据发现,IPdR作为放射增敏剂效果良好,具有可口服、毒性较低的特点。目前该药物已经完成Ⅰ期临床,即将开展Ⅱ临床试验,有望成为一种新型的口服放射增敏药物。

Research Progress and Mechanism of Action on Radiosensitizer IPdR

Objective: Radiosensitizer IPdR (5-iodo-2-pyrimidin-2''deoxyribose) was reviewed for providing ideas and references of the development of IPdR. Methods: Through the review of related literature at home and abroad, analysis of properties, mechanism and advantages of IPdR as a radiotherapy sensitization, the pharmacodynamic and toxicological findings of IPdR and the latest clinical advances in phase I were summarized, Phase II clinical trials were conducted and safety assessment scheme was discussed. Results and Conclusion: IPdR, as a precursor compound of IUdR (5-iodo-2''deoxyuridine), is a halogenated nucleoside analog which can enter the body by oral administration. With catalysis of aldehyde oxidase, the IPdR in the blood is gradually converted into IUdR which binds to the DNA of tumor cells and increases the radiosensitivity of the lesion tissues, thus exerting the drug effect. According to the preliminary efficacy and toxicological data, IPdR showed good effect as a radiosensitizer and has the characteristics of oral administration and low toxicity. At present, the drug has completed Phase I clinical trial and is about to process further clinical trials. It is expected to become a new oral radiosensitizer.