A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor

Yoko Yashiroda1, Reika Okamoto, Kaori Hatsugai

  • 1Chemical Genomics Research Group/Chemical Genetics Laboratory, RIKEN Advanced Science Institute, Wako, Saitama 351-0198, Japan. ytyy@riken.jp

Insights

Researchers developed a novel yeast-based assay to screen for tankyrase 1 inhibitors, crucial for cancer therapy. This system successfully identified flavone as a potential inhibitor, paving the way for new drug discovery.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Yeast Genetics

Background:

  • Tankyrase 1, a poly(ADP-ribose) polymerase, is a key target in cancer therapy, particularly for BRCA-associated cancers.
  • Developing efficient screening systems for tankyrase 1 inhibitors is challenging due to difficulties in enzyme and substrate preparation.

Purpose of the Study:

  • To establish a robust cell-based assay system for detecting inhibitory activity against tankyrase 1.
  • To facilitate high-throughput screening for potential tankyrase 1 inhibitors.

Main Methods:

  • Utilized the fission yeast Schizosaccharomyces pombe as a model system.
  • Developed a growth restoration assay where compounds counteracting tankyrase 1 overexpression-induced growth defects were identified.
  • Performed high-throughput screening using robotics.

Main Results:

  • Overexpression of human tankyrase 1 gene induced a growth defect in Schizosaccharomyces pombe.
  • Identified flavone as a compound that restored yeast cell growth.
  • Confirmed that flavone inhibits poly(ADP-ribosyl)ation mediated by tankyrase 1 in yeast cells.

Conclusions:

  • The developed yeast-based system provides an efficient method for identifying tankyrase 1 inhibitory activity.
  • This assay is amenable to high-throughput screening, accelerating the discovery of novel tankyrase 1 inhibitors for cancer therapy.