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

doi:10.1038/s41467-026-76337-2

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Article

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

Nature communications - 27 Aug 2026

Yoshikawa Yoko, Kubota Hirokazu, Matsumoto Shigeyuki, Makino Yoshiteru, Kawamura Takashi, Yuki Hitomi, Sakai Naoki, Shibaike Akira, Okamura Megumi, Fujimoto-Sakisaka Wakako, Honda Kou, Horikawa Taisuke, Mori Ichiro, Okada Morihito, Horikawa Manabu, Horie Kazumasa, Koyanagi-Aoi Michiyo, Aoi Takashi, Kataoka Tohru, Okada Tomoyo, Tamura Atsuo, Honma Teruki, Kumasaka Takashi, Koyama Hiroo, Shima Fumi

Abstract excerpt

RAS, a frequently mutated cancer-driver gene, has been the focus of intensive research, with numerous inhibitors developed to target RAS and its signalling molecules. With the advent of approved subtype-specific RAS inhibitors targeting KRASG12C mutation, the development of RAS inhibitors that are effective regardless of RAS mutation status is the next major challenge to address clinically prevalent RAS mutations...

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