Targeting MutT Homolog 1 (MTH1) for Breast Cancer Suppression by Using a Novel MTH1 Inhibitor MA-24 with Tumor-Selective Toxicity.

ABSTRACT:

Background

Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells need MTH1 for survival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer.

Methods

MA-24 was screened by malachite green colorimetric assay for MTH1 inhibitors and the kinetic characteristics of MA-24 were assessed. The features of MA-24's binding with MTH1 were ascertained through molecular docking, and the cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay, and Western blot confirmed the intracellular target and mechanism of MA-24.

Results

MA-24 shows potent antitumor bioactivity both in vitro and in vivo. MA-24 compe

SUBMITTER: Kang N 

PROVIDER: S-EPMC10974945 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature