Bioreductive药物:从概念到诊所。

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部SR,考恩RL,威廉姆斯KJ

Bioreductive药物:从概念到诊所。

肿瘤防治杂志(R科尔Radiol)。2007年8月,19 (6):427 - 42。2007年5月4日Epub。

PubMed ID

17482438 (在PubMed

]

文摘

radiobiologists的关键问题之一是低氧放疗反应的重要性。本文地址的原因,主要是侧重于一个方面,bioreductive药物是专门设计的发展目标肿瘤细胞缺氧。四类化合物这一概念第一次被提出以来,已开发:醌类、硝基芳香化合物、脂肪族和heteroaromatic N-oxides。都两个特点:(1)他们要求激活和(2)缺氧激活依赖于特定的还原酶的存在。最有效的化合物显示能力增强的抗肿瘤疗效特工杀死better-oxygenated细胞,即辐射和标准细胞毒性化疗药物顺铂和环磷酰胺等。Tirapazamine (TPZ)是研究最广泛的铅化合物。后成功的临床前体内结合研究进入临床试验;20多个试验已经被报道。尽管TPZ增强一些标准方案,结果在某些组合变量和毒性增强。Banoxantrone (AQ4N)是另一个显示的代理承诺早在I / II期临床试验; the drug is well tolerated, is known to locate in the tumour and can be given in high doses without major toxicities. Mitomycin C (MMC), which shows some bioreductive activation in vitro, has been tested in combination trials. However, it is difficult to assign the enhancement of its effects to targeting of the hypoxic cells because of the significant level of its hypoxia-independent toxicity. More specific analogues of MMC, e.g. porfiromycin and apaziquone (EO9), have had variable success in the clinic. Other new drugs that have good pre-clinical profiles are PR 104 and NLCQ-1; data on their clinical safety/efficacy are not yet available. This paper reviews the pre-clinical data and discusses the clinical studies that have been reported.

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药物

Banoxantrone