Yizhen Yin, Fener Chen. Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives[J]. Acta Pharmaceutica Sinica B, 2020, 10(12): 2259-2271

Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives
Yizhen Yina, Fener Chena,b,c
a Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China;
b Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, China;
c Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, China
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.
Key words:    Oxidized nucleotide    MTH1    Inhibitor    Anticancer    DNA repair   
Received: 2019-12-12     Revised: 2020-02-11
DOI: 10.1016/j.apsb.2020.02.012
Funds: This work was funded by the grant from the National Natural Science Foundation of China (81903425, to Yizhen Yin).
Corresponding author: Fener Chen,
Author description:
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Yizhen Yin
Fener Chen

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