Targeting human MutT homolog 1 (MTH1) for cancer eradication: current progress and perspectives.
10.1016/j.apsb.2020.02.012
- Author:
Yizhen YIN
1
;
Fener CHEN
1
Author Information
1. Institute of Pharmaceutical Science and Technology, Zhejiang University of Technology, Hangzhou 310014, China.
- Publication Type:Review
- Keywords:
AI, 7-azaindole;
AID, 7-azaindazole;
AP, aminopyrimidine;
AQ, amidoquinolines;
AZ, 2-aminoquinazoline;
Anticancer;
CETSA, cellular thermal shift assay;
CR, cyclometalated ruthenium;
DDR, DNA damage response;
DNA repair;
F, fragment;
FP, farnesyl phenolic;
IC50, half-maximal inhibitory concentrations;
Inhibitor;
MMR, DNA mismatch repair;
MTH1;
MTH1, human MutT homolog 1;
NSCLC, non-small cell lung cancer;
Oxidized nucleotide;
P, purinone;
PDT, photodynamic therapy;
PM, purinone macrocycle;
Pu, purine;
ROS, reactive oxygen species;
TLR7, Toll-like receptor 7;
TPP, thermal proteome profiling;
TS-FITGE, thermal stability shift-based fluorescence difference in two-dimensional gel electrophoresis
- From:
Acta Pharmaceutica Sinica B
2020;10(12):2259-2271
- CountryChina
- Language:English
-
Abstract:
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.
