RAS: A New Strategy to Block Cancer Proliferation Signals via “Remote Control”

August 28, 2026

Development of a small-molecule compound that alters the “shape” of RAF to suppress a wide range of RAS-related cancers

Kobe University, in collaboration with groups at RIKEN CSRS, RIKEN Center for Integrative Medical Sciences, and the Japan Synchrotron Radiation Research Institute, has developed a small-molecule compound that inhibits RAS signaling involved in cancer proliferation through a novel mechanism.

In many cancers, mutations in RAS proteins cause cell proliferation signals to be continuously transmitted. The newly developed compound binds not to RAS itself, but to a site on the RAF protein that is distinct from the RAS-binding site—the site where RAF receives signals from RAS. This causes a structural change in RAF, and as this effect is transmitted to the binding interface with RAS, the binding between RAS and RAF is disrupted. Through this “allosteric action,” the researchers have elucidated a novel mechanism that effectively “remotely controls” the RAS signaling.

This compound demonstrated antitumor effects not only against cancers harboring various RAS mutations—such as KRAS, NRAS, and HRAS—but also against malignant melanoma that is resistant to existing BRAF inhibitors. It is expected to lead to the development of new therapies for a wide range of RAS-related cancers and drug-resistant cancers.

 

Original article

Nature Communications　DOI: 10.1038/s41467-026-76337-2

Y. Yoshikawa, H. Kubota, S. Matsumoto, Y. Makino, T. Kawamura, H. Yuki, N. Sakai, A. Shibaike, M. Okamura, W. Fujimoto-Sakisaka, K. Honda, T. Horikawa, I. Mori, M. Okada, M. Horikawa, K. Horie, M. Koyanagi-Aoi, T. Aoi, T. Kataoka, T. Okada, A. Tamura, T. Honma, T. Kumasaka, H. Koyama, F. Shima,

"Small-molecule RAS/RAF inhibitors target RAS-driven cancers via allosteric RAF disruption".

Contact

Hiroo Koyama
Unit Leader
Drug Discovery Chemistry Platform Unit Team