In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders
Sign Up to like & getrecommendations! Published in 2023 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.2c01479
Abstract: The KRAS switch-II pocket (SII-P) has proven to be one of the most successful tools for targeting KRAS with small molecules to date. This has been demonstrated with several KRAS(G12C)-targeting covalent inhibitors, already resulting in… read more here.
Keywords: switch pocket; water; conserved water; thr58 ... See more keywords
Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRASG12C Inhibitor
Sign Up to like & getrecommendations! Published in 2022 at "Journal of Medicinal Chemistry"
DOI: 10.1021/acs.jmedchem.2c01120
Abstract: Activating mutations in KRAS are the most frequent oncogenic alterations in cancer. The oncogenic hotspot position 12, located at the lip of the switch II pocket, offers a covalent attachment point for KRASG12C inhibitors. To… read more here.
Keywords: switch pocket; krasg12c inhibitor; pocket; vivo active ... See more keywords
KRAS is vulnerable to reversible switch-II pocket engagement in cells
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DOI: 10.1038/s41589-022-00985-w
Abstract: Current small-molecule inhibitors of KRAS(G12C) bind irreversibly in the switch-II pocket (SII-P), exploiting the strong nucleophilicity of the acquired cysteine as well as the preponderance of the GDP-bound form of this mutant. Nevertheless, many oncogenic… read more here.
Keywords: spectroscopy; switch pocket; kras vulnerable; reversible switch ... See more keywords
Inhibition of RAS-driven signaling and tumorigenesis with a pan-RAS monobody targeting the Switch I/II pocket
Sign Up to like & getrecommendations! Published in 2022 at "Proceedings of the National Academy of Sciences of the United States of America"
DOI: 10.1073/pnas.2204481119
Abstract: Significance RAS is mutated in nearly 20% of human cancers and has few direct, efficacious inhibitors. Here, we developed a synthetic protein, JAM20, to discover potential regions on RAS that may be used for inhibition.… read more here.
Keywords: switch; switch pocket; targeting switch; inhibition ras ... See more keywords