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Updated: Feb 15, 2026

An Ex vivo Model to Study Hormone Action in the Human Breast
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An Ex vivo Model to Study Hormone Action in the Human Breast

Published on: January 8, 2015

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Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

Brent D G Page1, Nicholas C K Valerie2, Roni H G Wright3,4

  • 1Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Solna, SE-171 21, Sweden. brent.page@scilifelab.se.

Nature Communications
|January 19, 2018
PubMed

Insights

This study reveals NUDT5

Area of Science:

  • Biochemistry and Molecular Biology
  • Cancer Research

Background:

  • NUDIX hydrolases are key nucleotide-metabolizing enzymes.
  • NUDT5 is involved in ADP-ribose metabolism and regulates gene expression and proliferation in breast cancer.

Purpose of the Study:

  • To further elucidate the physiological roles of NUDT5 substrates.
  • To investigate the necessity of NUDT5 in breast cancer cell gene regulation and proliferation.
  • To identify and characterize novel NUDT5 inhibitors.

Main Methods:

  • Cellular thermal shift assay (CETSA) for inhibitor optimization.
  • Analysis of ADP-ribose metabolism and oxidized nucleotide sanitation.
  • Assessment of NUDT5's role in progestin-dependent processes.

Main Results:

  • NUDT5's role in ADP-ribose metabolism is confirmed, distinct from oxidized nucleotide sanitation.
  • The NUDT5 inhibitor TH5427 effectively engages cellular targets.
  • TH5427 inhibits progestin-dependent ATP synthesis, chromatin remodeling, gene regulation, and proliferation in breast cancer cells.

Conclusions:

  • NUDT5 is crucial for gene regulation and proliferation in breast cancer.
  • TH5427 is a potent and targeted inhibitor of NUDT5.
  • TH5427 serves as a valuable tool for studying NUDT5 activity and ADP-ribose metabolism.

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