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<p>The paper gives a detailed account of the most recent advances in the development of inhibitors for mutant forms of GTPase KRAS, which plays a key role in the pathogenesis of various cancers. The complexity and limitations of targeting KRAS caused by its structural features and high mutation rate are highlighted. The review focuses on pan-selective inhibitors that can target several KRAS mutations, which is important for overcoming tumor resistance to therapy. Examples of promising molecular structures are given and mechanisms of action and possible causes for selectivity are analyzed.</p>

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Analysis of binding modes for direct pan-specific inhibition of mutant forms of guanosine triphosphatase KRAS and prospects for targeting various allosteric sites

  • 期刊论文

  • 发表日期：

    2026年1月1日

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  • D. O. Shkil,
  • I. A. Eliseev,
  • R. A. Ivanov,
  • K. V. Balakin

摘要

The paper gives a detailed account of the most recent advances in the development of inhibitors for mutant forms of GTPase KRAS, which plays a key role in the pathogenesis of various cancers. The complexity and limitations of targeting KRAS caused by its structural features and high mutation rate are highlighted. The review focuses on pan-selective inhibitors that can target several KRAS mutations, which is important for overcoming tumor resistance to therapy. Examples of promising molecular structures are given and mechanisms of action and possible causes for selectivity are analyzed.