Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.
Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.
复制标题
靶向人类 MutT 同源物 1 (MTH1) 来根除癌症：当前进展和前景
DOI：
10.1016/j.apsb.2020.02.012
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Chen F
中科院分区：
文献类型：
--
作者：
Yin Y;Chen F
由于加速的代谢在癌细胞中产生比正常细胞中发现的ROS水平高得多的活性氧（ROS）水平，因此最近证明了净化氧化核苷酸池的人MutT同系物1（MTH1）对癌细胞的存活至关重要，但不是正常细胞增殖所必需的。因此，已经开发了数十种MTH1抑制剂，目的是通过在癌细胞中积累氧化损伤来抑制癌症生长。虽然几种抑制剂确实被证实是有效的，但一些抑制剂未能杀死癌细胞，使MTH1作为癌症根除的可行靶点变得复杂。本文综述了MTH1抑制剂作为候选药物的研究现状，并根据其结构对MTH1抑制剂进行了分类，展望了MTH1靶向治疗癌症的前景。人类MutT同系物1（MTH1）作为癌细胞生存所必需的酶，近年来被证明是一个很有前途的肿瘤治疗靶点。本文综述了近年来MTH1抑制剂的研究进展，并展望了其治疗潜力。
Since accelerated metabolism produces much higher levels of reactive oxygen species (ROS) in cancer cells compared to ROS levels found in normal cells, human MutT homolog 1 (MTH1), which sanitizes oxidized nucleotide pools, was recently demonstrated to be crucial for the survival of cancer cells, but not required for the proliferation of normal cells. Therefore, dozens of MTH1 inhibitors have been developed with the aim of suppressing cancer growth by accumulating oxidative damage in cancer cells. While several inhibitors were indeed confirmed to be effective, some inhibitors failed to kill cancer cells, complicating MTH1 as a viable target for cancer eradication. In this review, we summarize the current status of developing MTH1 inhibitors as drug candidates, classify the MTH1 inhibitors based on their structures, and offer our perspectives toward the therapeutic potential against cancer through the targeting of MTH1. As an essential enzyme for the survival of cancer cells, human MutT homolog 1 (MTH1), was recently demonstrated as a promising target for cancer eradication. This review summarizes the current progress of developing MTH1 inhibitors with various structures as drug candidates and presents our perspectives toward the therapeutic potential.
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