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The KRASG12D inhibitor MRTX1133 elucidates KRAS-mediated oncogenesis

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The identification of KRASG12C inhibitors has reignited interest in targeting RAS proteins. This work describes the discovery of the KRASG12D-specific inhibitor MRTX1133 and demonstrates the feasibility of potently and selectively targeting this oncogenic variant. MRTX1133 treatment markedly inhibited KRAS-dependent signaling and induced tumor regression in xenograft models harboring the KRASG12D mutation.

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Fig. 1: MRTX1133 potently inhibits both the active state and the inactive state of KRASG12D and has anti-cancer activity in KRASG12D-bearing human tumor xenograft models.

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This is a summary of: Hallin, J. et al. Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor. Nat. Med. https://doi.org/10.1038/s41591-022-02007-7 (2022).

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The KRASG12D inhibitor MRTX1133 elucidates KRAS-mediated oncogenesis. Nat Med 28, 2017–2018 (2022). https://doi.org/10.1038/s41591-022-02008-6

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  • DOI: https://doi.org/10.1038/s41591-022-02008-6

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