Article
Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer.
Cancer cell - 8 Jul 2024
Zhou Caicun, Li Chongyang, Luo Libo, Li Xin, Jia Keyi, He Ning, Mao Shiqi, Wang Wanying, Shao Chuchu, Liu Xinyu, Huang Kan, Yu Yaxin, Cai Xinlei, Chen Yingxue, Dai Zican, Li Wei, Yu Jia, Li Jiayu, Shen Feng, Wang Zaiyong, He Feng, Sun Xing, Mao Rongfu, Shi Wei, Zhang Jun, Jiang Tao, Zhang Zhe, Li Fei, Ren Shengxiang
Abstract excerpt
KRAS G12D is the most frequently mutated oncogenic KRAS subtype in solid tumors and remains undruggable in clinical settings. Here, we developed a high affinity, selective, long-acting, and non-covalent KRAS G12D inhibitor, HRS-4642, with an affinity constant of 0.083 nM. HRS-4642 demonstrated robust efficacy against KRAS G12D-mutant cancers both in vitro and in vivo. Importantly, in a phase 1 clinical trial,...
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