Discovery of a compound that attenuates tumor growth, metastasis, and endotoxic shock

October 8, 2021

A joint research group of the Institute of Biomedical Science, Kansai Medical University and RIKENCSRS identified a compound that inhibits Mint3, a molecule involved in cancer development and inflammatory diseases, and showed that the Mint3 inhibitor suppresses tumor growth, metastasis, and endotoxic shock in mouse models.

Hypoxia-inducible factor-1 (HIF-1), an important transcription factor involved in the response of cells to oxygen levels, accumulates under hypoxia and promotes the expression of genes necessary to adapt to hypoxia. While HIF-1 plays an important role in the functions of normal organs, such as hematopoiesis and stem cell function maintenance, it has been shown to exacerbate cancer and inflammatory diseases. Although many studies have shown that experimental inhibition of HIF-1 suppresses cancer and inflammatory diseases, it is difficult to develop drugs targeting HIF-1 because HIF-1 is also involved in the functions of normal organs. The research group had already identified Mint3 as a molecule that activates HIF-1 only in certain cells, such as cancer cells and macrophages, and had found that Mint3, as in the case with HIF-1, is involved in cancer and inflammatory diseases. However, no compound that suppresses Mint3 functions has been found, and it has not been known whether Mint3 inhibitors are actually effective for cancer and inflammatory diseases.

The results of this research are expected to contribute to development of cancer drugs and inflammatory disease drugs targeting Mint3.

Original article
Communications Biology doi:10.1038/s42003-021-02701-1
T. Sakamoto, Y. Fukui, Y. Kondoh, K. Honda, Takeshi Shimizu, T. Hara, T. Hayashi, Y. Saitoh, Y. Murakami, J. Inoue, S. Kaneko, H. Osada, M. Seiki,
"Pharmacological inhibition of Mint3 attenuates tumour growth, metastasis, and endotoxic shock".
Yasumitsu Kondoh; Senior Research Scientist
Hiroyuki Osada; Group Director
Chemical Biology Research Group