Chemoselective Covalent Modification of K-Ras(G12R) with a Small Molecule Electrophile

Zhang, Ziyang, Morstein, Johannes, Ecker, Andrew K., Guiley, Keelan Z., Shokat, Kevan M.·2022·Journal of the American Chemical Society
DOI 10.1021/jacs.2c05377

Cited by (160)

Items 101–160 of 160

  1. Thermodynamic characterisation of covalent ligand binding
    Rebecca Hertzman, Maayan Lavie, Almog Nadir, Ronen Gabizon, Nir London · 2026 · British Journal of Pharmacology
  2. Protein State‐Dependent Chemical Biology
    Kevin A. Scott, Tiffany L. Zhang, Sarah Y. Xi, Bryan Ngo, Ekaterina V. Vinogradova · 2023 · Israel Journal of Chemistry
  3. Insights into direct KRAS inhibition strategies for cancer treatment
    Tong Li, Chenglei Gu, Chen Zhou, Chunqin Mao, Kan Yang, Jinyi Xu, Tulin Lu, Jichao Chen · 2024 · Future Medicinal Chemistry
  4. Targeting KRASG13C with cyclic linker based inhibitors to explore warhead orientation
    Tonia Kirschner, João Rodriguez, Emerson Gonçalves Moreira, Janina Niggenaber, Jonas D. Warmuth, Hugo Verli, Matthias Philipp Müller, Daniel Rauh · 2025 · Scientific Reports
  5. High-Throughput Cell-Based Screening of Small Molecule KRAS Signaling Inhibitors Using a Homogeneous Time-Resolved Fluorescence (HTRF) Assay
    Brian P. Smith, Megan Rigby, Roger Ma, Anna E. Maciag · 2024 · Methods in molecular biology
  6. Determining KRAS4B-Targeting Compound Specificity by Top–Down Mass Spectrometry
    Robert A. D’Ippolito, Grace M. Scheidemantle, Dana Rabara, Maria Abreu Blanco, Nitya Ramakrishnan, Stephanie R. T. Widmeyer, Simon Messing, David Turner, Anna E. Maciag, Andrew G. Stephen et al. · 2024 · Methods in molecular biology
  7. Advancing KRAS drug discovery: A deep dive into biochemical, biophysical, and cellular assays for the identification and optimization of KRAS inhibitors
    Anthony N. Milin, John P. Giddens, Abby Marquez · 2024 · Elsevier eBooks
  8. Small‐Molecule KRAS Inhibitors by Tyrosine Covalent Bond Formation
    Alexander D. Landgraf, Robert Brenner, Mona K. Ghozayel, Khuchtumur Bum‐Erdene, Giovanni González-Gutiérrez, Samy O. Meroueh · 2025 · ChemMedChem
  9. Copper-Mediated Oxidative Coupling of Difluoromethyl Bromides/Chlorides with Primary Amines: Direct Synthesis of α-Ketoamides
    Feng Jun Jin, Guangzhao Xu, Fahui Li, Weilong Cao, Binzhuo Liu, Yuanyuan Xu, Ya‐Nan Chu, Weiguo Song, Peng Peng, Kai‐Rui Feng · 2025 · The Journal of Organic Chemistry
  10. RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types
    Zahra Davoudi, Thomas Steven Dexheimer, Nathan P. Coussens, Thomas E. Silvers, Raymond G. Fox, Samantha B. Kemp, Poorva Juneja, Joel Morris, Melinda G. Hollingshead, Naoko Takebe et al. · 2025 · Cancer Research Communications
  11. Quantitative Reactivity Profiling of Functional Arginine Residues in Human Cancer Cell Line Proteomes
    Wenbo Zhao, Yuliang Tang, Yihui Gao, Qi Ding, Qiang Li, Wenyang Li, Xiaoguang Lei · 2025 · Angewandte Chemie
  12. Targeting RAS for Cancer Treatment: What a Long, Strange Trip It's Been
    Adrienne D. Cox, Channing J. Der · 2025 · Annual Review of Cancer Biology
  13. Targeting enzymes with covalent warheads: Beyond cysteine
    Disha Patel, Anshul Sharma, Dustin Duncan · 2025 · Elsevier eBooks
  14. The evolving landscape of RAS-targeted therapies
    Sandra Misale · 2025 · Nature Cancer
  15. Targeting a Pleckstrin Homology Domain with a Lysine-Reactive Covalent Binder
    Rebekah M. West, Radu Costin Bizga Nicolescu, P. Brear, James Mark Wagstaff, Beata K. Blaszczyk, Tomáš Deingruber, Matthew G. Sanders, Francisco Javier Pérez-Areales, David R. Spring, Marko Hyvönen · 2026 · Journal of Medicinal Chemistry
  16. Mechanistic insights into Ras-catalyzed GTP hydrolysis: conformational dynamics, catalytic mechanisms, and emerging therapeutic strategies
    Carsten Kötting, Till Rudack, Klaus Bernhard Gerwert · 2025 · Biological Chemistry
  17. Analysis of binding modes for direct pan-specific inhibition of mutant forms of guanosine triphosphatase KRAS and prospects for targeting various allosteric sites
    Dmitrii O. Shkil, Ilya A. Eliseev, R. A. Ivanov, K. V. Balakin · 2026 · Russian Chemical Bulletin
  18. Single‐Sequence Deep Learning Delivers Crystal‐Quality Models of Covalent K‐Ras G12 Hotspot Complexes
    Sungwon Jung, Qinheng Zheng, Kevan M. Shokat · 2026 · IUBMB Life
  19. Brønsted-basic small molecules activate GTP hydrolysis in KRAS-Q61 mutants
    Yecheng Wang, Si‐Cong Chen, Yang Cao, Yang Wu, Zhongda Shi, Celine D. Wang, Michael A. Norinskiy, Hasan Celik, Ziyang Zhang · 2026 · Nature Chemical Biology
  20. Ninhydrin as a Covalent Warhead for Chemical Proteomic-Enabled Discovery and Selective Engagement of Reactive Arginines
    Andrew K. Ecker, Andreas Langen, Chloe S. Fields, José L. Montaño, Minh Tran, Ian B. Seiple, Balyn W. Zaro · 2026 · ACS Central Science
  21. Mutations influence the conformational dynamics of the GDP/KRAS complex
    Congcong Shen, Jie Yin, Min Wang, Zhiping Yu, Xin Yu Xu, Zhong-Shun Zhou, Yingshi Hu, Caijuan Xia, Guodong Hu · 2024 · Journal of Biomolecular Structure and Dynamics
  22. The evolution of RAS structural biology
    Dhirendra K. Simanshu, John E. Knox · 2024 · Elsevier eBooks
  23. Strain-release alkylation of Asp12 enables mutant selective GTP-state targeting of K-Ras(G12D)
    Qinheng Zheng, Ziyang Zhang, Keelan Z. Guiley, Kevan M. Shokat · 2023 · bioRxiv (Cold Spring Harbor Laboratory)
  24. Data from Facts and Hopes on RAS Inhibitors and Cancer Immunotherapy
    Jesse Boumelha, Míriam Molina‐Arcas, Julian Downward · 2023
  25. Combinations of RAS pathway inhibitors with targeted agents are active in spheroids of patient-derived cells with oncogenic KRAS variants from multiple cancer types
    Zahra Davoudi, Thomas Steven Dexheimer, Nathan P. Coussens, Thomas E. Silvers, Joel Morris, Naoko Takebe, James H. Doroshow, Beverly A. Teicher · 2024 · bioRxiv (Cold Spring Harbor Laboratory)
  26. A Modular Platform for the Optogenetic Control of Small GTPase Activity in Living Cells Reveals Long-Range RhoA Signaling
    Benjamin M. Faulkner, Yuchen He, Daniel Sitrin, Linda Ziamanesh, Cliff I. Stains · 2025 · bioRxiv (Cold Spring Harbor Laboratory)
  27. Brønsted-basic small molecules activate GTP hydrolysis in Ras Q61 mutants
    Yecheng Wang, Si‐Cong Chen, Yang Wu, Yan Cao, Zhongda Shi, Michael A. Norinskiy, Celine D. Wang, Hasan Celik, Ziyang Zhang · 2025 · bioRxiv (Cold Spring Harbor Laboratory)
  28. Modern Methods for Late‐stage Peptide Modification
    Yuxuan Ding, Zachary T. Ball · 2025 · Peptide Science
  29. ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing
    Jason Tse, William R. Brothers, Rachel E. Hayward, Sabrina Barbas, Kai Sheng, Kathryn R. Spencer, Kristen E. DeMeester, Evert Njomen, James R. Williamson, David R. Liu et al. · 2026 · bioRxiv (Cold Spring Harbor Laboratory)
  30. Targeting KRAS G12R with α,β-Diketoamides
    Dirk H. Trauner, Klaus-Peter Ruehmann · 2022 · Synfacts
  31. Well-tempered metadynamics calculations of free energy surfaces of benzothiadiazine derivatives in aqueous solution
    Zheyao Hu, Jordi Martı́ · 2023 · bioRxiv (Cold Spring Harbor Laboratory)
  32. Data from Facts and Hopes on RAS Inhibitors and Cancer Immunotherapy
    Jesse Boumelha, Míriam Molina‐Arcas, Julian Downward · 2023
  33. A Suite of Biochemical and Cell-Based Assays for the Characterization of KRAS Inhibitors and Degraders
    Medhanie Kidane, Rene M. Hoffman, Jennifer K. Wolfe-Demarco, Ting-Yu Huang, Chi-Ling Teng, Luis M. Gonzalez Lira, Jennifer Lin‐Jones, Gabriel Pallares, Jane E. Lamerdin, Nicole B. Servant et al. · 2024 · bioRxiv (Cold Spring Harbor Laboratory)
  34. Standardized Parts for Activation of Small GTPase Signaling in Living Cells
    Yuchen He, Benjamin M. Faulkner, Meaghan A. Roberti, Dana K. Bassford, Cliff I. Stains · 2024 · Angewandte Chemie
  35. Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?
    Fiona M. Healy, Amy L. Turner, Vanessa Marensi, David J. MacEwan · 2024 · Frontiers in Pharmacology
  36. Emerging Technologies for Epigenetic Drug Discovery
    2024 · Royal Society of Chemistry eBooks
  37. Mass Spectrometry and Chemical Biology Approaches for Deconvoluting Epigenetic Targets
    Antony J. Burton, Ghaith M. Hamza, Anthony A. Iannetta, Eric Miele, Andrew X. Zhang · 2024 · Royal Society of Chemistry eBooks
  38. Conclusions: the future of RAS drug discovery
    Adrian L. Gill, Kevan M. Shokat · 2024 · Elsevier eBooks
  39. Targeting RAS and associated proteins
    Matthias Philipp Müller, Roger Sidney Goody, Daniel Rauh · 2025 · Elsevier eBooks
  40. Recent highlights in covalent inhibitor design
    Kristen A. Marino, Robert Nicewonger, Hongjun Zhang, Atli Thorarensen · 2025 · Elsevier eBooks
  41. Impact of Mutational Status on Intracellular Effects of Cell‐Permeable CaaX Peptides in Pancreatic Cancer Cells
    Merlin Klußmann, Martin Matijass, Ines Neundorf · 2025 · ChemBioChem
  42. Translating Basic Science Discoveries into Clinical Advances: Highlights from the EACR-AACR-IACR 2024 Conference in Celebration of Irish Association for Cancer Research’s 60th Anniversary
    Seodhna M. Lynch, Cathy E. Richards, Aisling Ui Mhaonaigh, Niamh Lynam‐Lennon, Alex J. Eustace, Emma H. Allott, Tracy Robson, Simone Marcone · 2025 · Cancers
  43. Krasg12d Selective Vhl-Protac with Sparing Kraswt and Other Kras Mutants
    Taebo Sim, Eunhye Jeon, Chan Kim, Minjoo Ko, Taeyul K. Kim, Juhyeon Bae, Jae Won Oh, Kwang Pyo Kim, Han Sang Kim · 2025 · SSRN Electronic Journal
  44. Attempts to Achieve Targeted Covalent Inhibition of Hsp90 β
    Terin D’Amico, Tyelor S. Reynolds, Michael A. Serwetnyk, Brian S. J. Blagg · 2026 · Chemical Biology & Drug Design
  45. Design of α-ketothioesters as efficient reagents for arginine modification
    Yunru Wang, Liqing Zhu, Weiguo Zou, Wanyi Zou, Qingqing Tang, Yaping Zhou, Shiqi Liu, Bing Zhou, Lanning Zhao, Yaxi Yang · 2026 · Tetrahedron Letters
  46. RAS and KRAS Inhibitors in Cancer Therapeutic Mechanisms and Resistance: Scoping Review with ☸SAIMSARA
    SAIMSARA · 2026 · SAIMSARA Journal
  47. Expanding Addressable KRAS Mutations through the Structure- and Property-Based Design of Dual-State (GDP/GTP), Reversible Pan-KRAS Inhibitors
    Ryan P. Wurz, Jennifer R. Allen, John G. Allen, Albert K. Amegadzie, Ning Chen, Josephine Eshon, Kexue Li, Xiaofen Li, Yunxiao Li, Francesco Manoni et al. · 2026 · Journal of Medicinal Chemistry
  48. Induction of cuproptosis via targeting mitochondrial metabolism using dPTBD with potent therapeutic activity against KRAS-driven cancer
    Yichen Sun, Ming Song, Wenwen Ding, Qi Liu, Wenhua Lu, Bingling Luo, Ping Chen, Jing Yang, Yumin Hu, Shijun Wen et al. · 2026 · Cancer Letters
  49. Structure-based scaffold hopping reveals strategies to overcome oncogenic KIT and PDGFRA mutation-driven drug-resistance in GIST
    Tom Schulz, Maria Beerbaum, Andrea Scrima, Hannah Jantzen, Alina Teuber, Thomas Mühlenberg, L. Ebel, F. Garcia-Fossa, Amy L. George, N. Berner et al. · 2026 · Nature Communications
  50. Discovery of Arginine-Reactive Covalent Kinase Inhibitors Overcoming Clinical Drug Resistance
    Zuqin Wang, Xuan Wang, Hong Zhang, Jiahuan He, Lu Wang, Ling Li, Peng Chen, Jibo Kang, Xiaojuan Song, Zhengchao Tu et al. · 2026 · Journal of Medicinal Chemistry
  51. A Modular Optogenetic Split-Small GTPase Platform Reveals Long-Range RhoA Signaling
    Benjamin M. Faulkner, Yuchen He, Daniel Sitrin, Linda Ziamanesh, Cliff I. Stains · 2026 · ACS Chemical Biology
  52. BindingDB Entry 50021193: Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update.
    BindingDB · 2025 · UC San Diego
  53. BindingDB Entry 50019814: Annual review of KRAS inhibitors in 2022.
    BindingDB · 2024 · UC San Diego
  54. BindingDB Entry 50019872: Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.
    BindingDB · 2024 · UC San Diego
  55. BindingDB Entry 50018208: Design, Synthesis, and Bioevaluation of Pyrido[2,3-
    BindingDB · 2024 · UC San Diego
  56. BindingDB Entry 50023574: Reversible Small Molecule Multivariant Ras Inhibitors Display Tunable Affinity for the Active and Inactive Forms of Ras.
    BindingDB · 2026 · UC San Diego
  57. BindingDB Entry 50023817: Synthetic approaches and clinical application of KRAS inhibitors for cancer therapy.
    BindingDB · 2026 · UC San Diego
  58. BindingDB Entry 50021822: Structure-activity relationships of middle-size cyclic peptides, KRAS inhibitors derived from an mRNA display.
    BindingDB · 2025 · UC San Diego
  59. BindingDB Entry 50021521: Pitfalls and Considerations in Determining the Potency and Mutant Selectivity of Covalent Epidermal Growth Factor Receptor Inhibitors.
    BindingDB · 2025 · UC San Diego
  60. BindingDB Entry 50023188: Innovative design and potential applications of covalent strategy in drug discovery.
    BindingDB · 2026 · UC San Diego