Article
Discovery of a potent and orally available SOS1 inhibitor with antitumor efficacy in KRAS-mutant colorectal cancers.
Bioorganic chemistry - 5 Jul 2026
Liu Xingchen, Xiao Yuzhou, Tang Lingfeng, Zhou Yanmei, Zhao Jinhua, Zou Jiao, Zhou Yue, Teng Yaxin, Fan Xinyu, Qiu Jiahao, Xu Jing, Qiu Zhiqiang, Gou Kun, Luo Haoyue, Ren Yanyan, Pan Xiaodan, Song Jialing, Xu Wenjing, Gao Ping, Ren Bo, Zhou Xia, Cen Xiaobo, Luo Youfu, Zhao Yinglan
Abstract excerpt
As a key guanine nucleotide exchange factor, SOS1 is an attractive therapeutic target for KRAS-driven colorectal cancer. In this study, based on the co-crystal structure of SOS1 in complex with BI-68BS, we developed a high-affinity fluorescent tracer TRR2 (KD = 0.134 μM), and established a robust fluorescence polarization assay for the profiling of SOS1 inhibitors. Subsequent structure-based optimization yielded...
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