ArticleJournal of medicinal chemistry2022
Fragment Optimization of Reversible Binding to the Switch II Pocket on KRAS Leads to a Potent, In Vivo Active KRAS
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Article in Journal of medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
5.9field-weighted citation impact, top 2% of its field
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Who cites it
35 citing papers in PubMed, 75 citations in OpenAlex.
- Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants.Nature chemical biology · 2026Article
- Targeted therapeutic strategies forTranslational lung cancer research · 2026Review
- Unveiling the KRAS Relationship between Affinity and Dynamics: A Molecular Simulations Study.Journal of chemical information and modeling · 2026Article
- Disulfide tethering reveals cryptic pockets in oncogenic KRAS.Communications chemistry · 2026Article
- Pan-KRAS inhibition: unlocking broad-spectrum targeted therapy forCancer biology & medicine · 2026Article
- Covalent inhibitor design confers activity against both GDP- and GTP-bound forms of KRAS G12C.Nature communications · 2026Article
- Evolution of direct RAS inhibitors: from undruggable target to clinical breakthroughs.Molecular cancer · 2025Review
- Discovery of BI-2493, a Pan-KRAS Inhibitor ShowingJournal of medicinal chemistry · 2025Article
- ADMET-Guided Docking and GROMACS Molecular Dynamics ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations.Scientific reports · 2025Article
- Response and Resistance to RAS Inhibition in Cancer.Cancer discovery · 2025Review
- Tumour-agnostic kinase inhibitors.Nature reviews. Drug discovery · 2025Review
- Switching It up with New KRAS Inhibitors.Journal of medicinal chemistry · 2025Review
- Size-Dependent Target Engagement of Covalent Probes.Journal of medicinal chemistry · 2025Article
- Drugging Challenging Cancer Targets Using Fragment-Based Methods.Chemical reviews · 2025Review
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Identification of Structurally Novel KRASJournal of medicinal chemistry · 2025Article
- First molecules to reactivate RASBMC cancer · 2025Article
- A New Dawn for Targeted Cancer Therapy: Small Molecule Covalent Binding Inhibitor Targeting K-Ras (G12C).Current medicinal chemistry · 2025Review
- Suite of Biochemical and Cell-Based Assays for the Characterization of Kirsten Rat Sarcoma (KRAS) Inhibitors and Degraders.ACS pharmacology & translational science · 2024Article
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Authors and funding
27 authors at 2 institutions in 2 countries.
Joachim BrökerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.ORCID 0000-0002-7371-8481
Alex G WatersonDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.ORCID 0000-0002-0153-5723
Chris SmethurstBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Dirk KesslerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.ORCID 0000-0001-6808-9011
Jark BöttcherBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Moriz MayerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Gerhard GmaschitzBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Jason PhanDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.
Andrew LittleDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.
Jason R AbbottDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.ORCID 0000-0002-2291-2903
Qi SunDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.
Michael GmachlBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Dorothea RudolphBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Heribert ArnhofBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Klaus RumpelBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Fabio SavareseBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Thomas GerstbergerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Nikolai MischerikowBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Matthias TreuBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Lorenz HerdeisBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Tobias WunbergBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Andreas GollnerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.ORCID 0000-0002-4347-8296
Harald WeinstablBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.ORCID 0000-0003-1308-2730
Andreas MantoulidisBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Oliver KrämerBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.
Darryl B McConnellBoehringer Ingelheim RCV GmbH & Co. KG, Dr. Boehringer Gasse 5-11, A-1121 Vienna, Austria.ORCID 0000-0002-2537-3458
Stephen W FesikDepartment of Biochemistry, Vanderbilt University School of Medicine, 2215 Garland Avenue, 607 Light Hall, Nashville, Tennessee 37232-0146, United States.ORCID 0000-0001-5957-6192
Boehringer Ingelheim (Austria) · ATVanderbilt University · US
Funding
The Vanderbilt Molecular Target Discovery and Development CenterRC2CA148375 · NCI · VANDERBILT UNIVERSITY · PI MARNETT, LAWRENCE J. · 2009 to 2010
$4.7MExpanding the druggable genomeDP1OD006933 · OD · VANDERBILT UNIVERSITY · PI FESIK, STEPHEN W. · 2010 to 2011
$1.5MNCI NIH HHS RC2 CA148375NIH HHS DP1 OD006933
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 KRAS
Indexed as
NeoplasmsProto-Oncogene Proteins p21(ras)CysteineGenes, rasHumansMutationCysteineKRAS protein, humanProto-Oncogene Proteins p21(ras)
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