Discovery of N-(1-Acryloylazetidin-3-yl)-2-(1 H-indol-1-yl)acetamides as Covalent Inhibitors of KRASG12C

Targeting RAS signalling pathways in cancer therapy

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K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

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Drugging the undruggable RAS: Mission Possible?

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AACR Project GENIE: Powering Precision Medicine through an International Consortium

The AACR Project GENIE Consortium, The AACR Project GENIE Consortium, André, F., Arnedos, M., Baras, A. S., Baselga, J., Bedard, P. L., Berger, M. F., Bierkens, M., Calvo, F., et al. (2017) · Cancer Discovery · doi:10.1158/2159-8290.cd-17-0151 · Cited by 1,964 · see citing works

The Ras superfamily at a glance

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Ras oncogenes: split personalities

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Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor

Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172 · see citing works

Blocking Oncogenic Ras Signaling for Cancer Therapy

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Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state

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Direct small-molecule inhibitors of KRAS: from structural insights to mechanism-based design

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Site-directed ligand discovery

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Chemical and Computational Methods for the Characterization of Covalent Reactive Groups for the Prospective Design of Irreversible Inhibitors

Flanagan, M. E., Abramite, J. A., Anderson, D. P., AULABAUGH, A. E., Dahal, U. P., Gilbert, A. M., Li, C., Montgomery, J. I., Oppenheimer, S. R., Ryder, T. F., et al. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm501412a · Cited by 337 · see citing works

Novel Allosteric Sites on Ras for Lead Generation

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Systematic Study of the Glutathione (GSH) Reactivity ofN-Arylacrylamides: 1. Effects of Aryl Substitution

Cee, V. J., Volak, L. P., Chen, Y., Bartberger, M. D., Tegley, C. M., Arvedson, T., McCarter, J. D., Tasker, A. S., & Fotsch, C. H. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01018 · Cited by 164 · see citing works

High-Throughput Mass Spectrometric Analysis of Covalent Protein-Inhibitor Adducts for the Discovery of Irreversible Inhibitors: A Complete Workflow

Campuzano, I. D. G., Miguel, T. S., Rowe, T., Onea, D., Cee, V. J., Arvedson, T., & McCarter, J. D. (2015) · SLAS DISCOVERY · doi:10.1177/1087057115621288 · Cited by 64 · see citing works

Synthesis of Diverse N-Acryloyl Azetidines and Evaluation of Their Enhanced Thiol Reactivities

Palkowitz, M. D., Tan, B., Hu, H., Roth, K. D. W., & Bauer, R. A. (2017) · Organic Letters · doi:10.1021/acs.orglett.7b00788 · Cited by 23 · see citing works

Abstract 4455: Discovery of AMG 510, a first-in-human covalent inhibitor of KRASG12C for the treatment of solid tumors

Lanman, B. A., Chen, J. J., Liu, L., Lopez, P., Pickrell, A. J., Reed, A. B., Wang, H., Achanta, P., Canon, J. R., Erlanson, D. A., et al. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-4455 · Cited by 9 · see citing works

Advances in covalent drug discovery

Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works

Discovery of a Covalent Inhibitor of KRAS ^G12C (AMG 510) for the Treatment of Solid Tumors

Lanman, B. A., Allen, J. R., Allen, J. G., Amegadzie, A. K., Ashton, K. S., Booker, S. K., Chen, J. J., Chen, N., Frohn, M. J., Goodman, G., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.9b01180 · Cited by 765 · see citing works

Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials

Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396 · see citing works

Crystal structure of human KRAS G12C covalently bound to a phthalazine inhibitor

Mohr, C. (2019) · Worldwide Protein Data Bank · doi:10.2210/pdb6pgo/pdb · Cited by 313 · see citing works

The current understanding of KRAS protein structure and dynamics

Pantsar, T. (2019) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2019.12.004 · Cited by 288 · see citing works

The path to the clinic: a comprehensive review on direct KRASG12C inhibitors

Kwan, A. K., Piazza, G. A., Keeton, A. B., & Leite, C. A. (2022) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-021-02225-w · Cited by 192 · see citing works

State-specific protein–ligand complex structure prediction with a multiscale deep generative model

Qiao, Z., Nie, W., Vahdat, A., Miller, T. F., & Anandkumar, A. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-024-00792-z · Cited by 178 · see citing works

Fragment‐based drug discovery—the importance of high‐quality molecule libraries

Bon, M., Bilsland, A. E., Bower, J. F., & McAulay, K. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13277 · Cited by 153 · see citing works

KRasG12C inhibitors in clinical trials: a short historical perspective

Goebel, L., Müller, M. P., Goody, R. S., & Rauh, D. (2020) · RSC Medicinal Chemistry · doi:10.1039/d0md00096e · Cited by 131 · see citing works

Advances in high‐throughput mass spectrometry in drug discovery

Dueñas, M. E., Heap, R. E., Leveridge, M. V., Annan, R. S., Büttner, F. H., & Trost, M. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202114850 · Cited by 124 · see citing works

Addressing Atropisomerism in the Development of Sotorasib, a Covalent Inhibitor of KRAS G12C: Structural, Analytical, and Synthetic Considerations

Lanman, B. A., Parsons, A. T., & Zech, S. G. (2022) · Accounts of Chemical Research · doi:10.1021/acs.accounts.2c00479 · Cited by 106 · see citing works

Profiling Sulfur(VI) Fluorides as Reactive Functionalities for Chemical Biology Tools and Expansion of the Ligandable Proteome

Gilbert, K. E., Vuorinen, A., Aatkar, A., Pogány, P., Pettinger, J., Grant, E. K., Kirkpatrick, J. M., Rittinger, K., House, D., Burley, G. A., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.2c00633 · Cited by 100 · see citing works

Small-Molecule Inhibitors Directly Targeting KRAS as Anticancer Therapeutics

Chen, H., Smaill, J. B., Liu, T., Ding, K., & Lu, X. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01312 · Cited by 100 · see citing works

A direct-to-biology high-throughput chemistry approach to reactive fragment screening

Thomas, R. P., Heap, R. E., Zappacosta, F., Grant, E. K., Pogány, P., Besley, S., Fallon, D. J., Hann, M. M., House, D., Tomkinson, N. C. O., et al. (2021) · Chemical Science · doi:10.1039/d1sc03551g · Cited by 92 · see citing works

Fragment-to-Lead Medicinal Chemistry Publications in 2019

Jahnke, W., Erlanson, D. A., de Esch, I. J. P., Johnson, C. N., Mortenson, P. N., Ochi, Y., & Urushima, T. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01608 · Cited by 73 · see citing works

Discovery of AZD4625, a Covalent Allosteric Inhibitor of the Mutant GTPase KRASG12C

Kettle, J. G., Bagal, S. K., Bickerton, S., Bodnarchuk, M. S., Boyd, S., Breed, J., Carbajo, R. J., Cassar, D. J., Chakraborty, A., Cosulich, S. C., et al. (2022) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c00369 · Cited by 69 · see citing works

Fragment-based drug discovery supports drugging ‘undruggable’ protein–protein interactions

Wang, Z.-Z., Shi, X.-X., Huang, G.-Y., Hao, G., & Yang, G. (2023) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2023.01.008 · Cited by 64 · see citing works

A Photoaffinity‐Based Fragment‐Screening Platform for Efficient Identification of Protein Ligands

Grant, E. K., Fallon, D. J., Hann, M. M., Fantom, K. G. M., Quinn, C. J., Zappacosta, F., Annan, R. S., Chung, C., Bamborough, P., Dixon, D. P., et al. (2020) · Angewandte Chemie International Edition · doi:10.1002/anie.202008361 · Cited by 59 · see citing works

Fragments: where are we now?

Osborne, J., Panova, S., Rapti, M., Urushima, T., & Jhoti, H. (2020) · Biochemical Society Transactions · doi:10.1042/bst20190694 · Cited by 59 · see citing works

Functionalized Scout Fragments for Site-Specific Covalent Ligand Discovery and Optimization

Crowley, V. M., Thielert, M., & Cravatt, B. F. (2021) · ACS Central Science · doi:10.1021/acscentsci.0c01336 · Cited by 53 · see citing works

The piperazine scaffold for novel drug discovery efforts: the evidence to date

Romanelli, M. N., Manetti, D., Braconi, L., Dei, S., Gabellini, A., & Teodori, E. (2022) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2022.2103535 · Cited by 53 · see citing works

Efficient Ligand Discovery Using Sulfur(VI) Fluoride Reactive Fragments

Aatkar, A., Vuorinen, A., Longfield, O., Gilbert, K. E., Heap, R. E., Wagner, C. D., Zappacosta, F., Rittinger, K., Chung, C., House, D., et al. (2023) · ACS Chemical Biology · doi:10.1021/acschembio.3c00034 · Cited by 51 · see citing works

Reactivity of Covalent Fragments and Their Role in Fragment Based Drug Discovery

McAulay, K., Bilsland, A. E., & Bon, M. (2022) · Pharmaceuticals · doi:10.3390/ph15111366 · Cited by 50 · see citing works

E3 Ligases Meet Their Match: Fragment-Based Approaches to Discover New E3 Ligands and to Unravel E3 Biology

Michaelides, I. N., & Collie, G. W. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.2c01882 · Cited by 50 · see citing works

Identification of Covalent Cyclic Peptide Inhibitors in mRNA Display

Iskandar, S. E., Chiou, L. F., Leisner, T. M., Shell, D. J., Norris-Drouin, J. L., Vaziri, C., Pearce, K. H., & Bowers, A. A. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.3c04833 · Cited by 43 · see citing works

KRAS(G12C)–AMG 510 interaction dynamics revealed by all-atom molecular dynamics simulations

Pantsar, T. (2020) · Scientific Reports · doi:10.1038/s41598-020-68950-y · Cited by 44 · see citing works

RAS degraders: The new frontier for RAS-driven cancers

Escher, T. E., & Satchell, K. J. F. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2023.03.017 · Cited by 35 · see citing works

Designing small molecules for therapeutic success: A contemporary perspective

Maurer, T. S., Edwards, M. P., Hepworth, D., Verhoest, P. R., & Allerton, C. M. N. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.09.017 · Cited by 37 · see citing works

Targeting RAS mutants in malignancies: successes, failures, and reasons for hope

Yang, H. S., Zhou, X., Fu, D., Le, C., Wang, J., Zhou, Q., Liu, X., Yuan, Y., Ding, K., & Xiao, Q. (2022) · 癌症：英文版 · doi:10.1002/cac2.12377 · Cited by 37 · see citing works

Small molecule Son of Sevenless 1 (SOS1) inhibitors: a review of the patent literature

Thompson, S. K., Buckl, A. K., Dossetter, A. G., Griffen, E., & Gill, A. L. (2021) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2021.1952984 · Cited by 35 · see citing works

Overexpression of ABCB1 Associated With the Resistance to the KRAS-G12C Specific Inhibitor ARS-1620 in Cancer Cells

Dong, X.-D., Zhang, M., Cai, C.-Y., Teng, Q.-X., Wang, J.-Q., Fu, Y.-G., Cui, Q., Patel, K., Wang, D.-T., & Chen, Z.-S. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.843829 · Cited by 29 · see citing works

In silico screening-based discovery of novel covalent inhibitors of the SARS-CoV-2 3CL protease

Xiong, M., Nie, T., Shao, Q., Li, M., Su, H., & Xu, Y. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114130 · Cited by 29 · see citing works

Small-Molecule RAS Inhibitors as Anticancer Agents: Discovery, Development, and Mechanistic Studies

Shetu, S. A., & Bandyopadhyay, D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23073706 · Cited by 28 · see citing works

A nonneglectable stereochemical factor in drug development: Atropisomerism

Yang, Y., Yang, B., & Li, L. (2022) · Chirality · doi:10.1002/chir.23497 · Cited by 28 · see citing works

Identification of novel Pyrrolo[2,3-d]Pyrimidine-based KRAS G12C inhibitors with anticancer effects

Song, Z., Lou, L., Fan, G., Liu, L., Yang, G., Liu, H., Chan, A. S. C., Zhang, X., & Xiong, X. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114907 · Cited by 28 · see citing works

Structure-based inhibitor design of mutant RAS proteins—a paradigm shift

Nyíri, K., Koppány, G., & Vértessy, B. G. (2020) · Cancer and Metastasis Reviews · doi:10.1007/s10555-020-09914-6 · Cited by 27 · see citing works

Targeting mutant KRAS

Erlanson, D. A., & Webster, K. R. (2021) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2021.02.010 · Cited by 28 · see citing works

Computational investigation to identify potent inhibitors of the GTPase-Kirsten RAt sarcoma virus (K-Ras) mutants G12C and G12D

Kumar, S. U., & Doss, C. G. P. (2021) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2021.104946 · Cited by 26 · see citing works

Expedited SARS‐CoV‐2 Main Protease Inhibitor Discovery through Modular ‘Direct‐to‐Biology’ Screening

Wilders, H., Biggs, G. S., Rowe, S. M., Cawood, E. E., Riziotis, I. G., Rendina, A. R., Grant, E. K., Pettinger, J., Fallon, D. J., Skehel, M. J., et al. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202418314 · Cited by 25 · see citing works

Fragment-Based Drug Discovery: Small Fragments, Big Impact − Success Stories of Approved Oncology Therapeutics

Khedkar, N. R., Sindkhedkar, M. D., & Joseph, A. (2025) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2025.108197 · Cited by 26 · see citing works

Optimizing drug design by merging generative AI with a physics-based active learning framework

Filella-Mercè, I., Molina, A., Díaz, L., Orzechowski, M., Berchiche, Y. A., Zhu, Y. M., Vilalta-Mor, J., Malo, L., Yekkirala, A. S., Ray, S. S., et al. (2025) · Communications Chemistry · doi:10.1038/s42004-025-01635-7 · Cited by 39 · see citing works

Discovery of novel SARS-CoV-2 3CL protease covalent inhibitors using deep learning-based screen

Wang, L., Yu, Z., Wang, S., Guo, Z., Sun, Q., & Lai, L. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114803 · Cited by 25 · see citing works

KRAS G12C fragment screening renders new binding pockets

Mathieu, M., Steier, V., Fassy, F., Delorme, C., Papin, D., Genêt, B., Duffieux, F., Bertrand, T., Delarbre, L., Le-Borgne, H., et al. (2021) · Small GTPases · doi:10.1080/21541248.2021.1979360 · Cited by 24 · see citing works

Covalent inhibitors of the GTPase KRASG12C: a review of the patent literature

Kettle, J. G., & Cassar, D. J. (2020) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2020.1709443 · Cited by 23 · see citing works

Identification of Structurally Novel KRAS G12C Inhibitors through Covalent DNA-Encoded Library Screening

Huang, D. S., Manoni, F., Sun, Z., Liu, R., Allen, J. R., Banerjee, A., Cee, V. J., Eshon, J., Frohn, M. J., Kaller, M. R., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c03071 · Cited by 22 · see citing works

Reactive fragments targeting carboxylate residues employing direct to biology, high-throughput chemistry

Thomas, R. P., Grant, E. K., Dickinson, E. R., Zappacosta, F., Edwards, L. J., Hann, M. M., House, D., Tomkinson, N. C. O., & Bush, J. T. (2023) · RSC Medicinal Chemistry · doi:10.1039/d2md00453d · Cited by 21 · see citing works

Covalent inhibitors: An ambitious approach for the discovery of newer oncotherapeutics

Cheke, R. S., & Kharkar, P. S. (2023) · Drug Development Research · doi:10.1002/ddr.22132 · Cited by 22 · see citing works

High-Throughput Covalent Modifier Screening with Acoustic Ejection Mass Spectrometry

Wen, X., Liu, C., Tovar, K., Curran, P., Richards, M. P., Agrawal, S., JOHNSTONE, R. M., Loy, R. E., Methot, J. L., Mansueto, M. S., et al. (2024) · Journal of the American Chemical Society · doi:10.1021/jacs.4c02377 · Cited by 20 · see citing works

Recent advances in the design of small molecular drugs with acrylamides covalent warheads

Liang, L., Zhang, Z., You, Q., & Guo, X. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117902 · Cited by 19 · see citing works

Modeling receptor flexibility in the structure-based design of KRASG12C inhibitors

Zhu, K., Li, C., Wu, K. Y., Mohr, C., Li, X., & Lanman, B. A. (2022) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-022-00467-0 · Cited by 16 · see citing works

Synthesis and anticancer screening of some novel Pd-catalysed 3-methyl indole based analogues on Mia PaCa-2 cell line

Rahman, A., Prashanth, N., Nippu, B. N., Kumaraswamy, H. M., Rajeshwara, A. N., & Satyanarayan, N. D. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.133211 · Cited by 15 · see citing works

DOX_BDW: Incorporating Solvation and Desolvation Effects of Cavity Water into Nonfitting Protein–Ligand Binding Affinity Prediction

Liu, J., Wan, J., Ren, Y., Shao, X., Xu, X., & Rao, L. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.3c00776 · Cited by 15 · see citing works

Identification of potential inhibitors, conformational dynamics, and mechanistic insights into mutant Kirsten rat sarcoma virus (G13D) driven cancers

Tayubi, I. A., Kumar, S. U., & Doss, C. G. P. (2022) · Journal of Cellular Biochemistry · doi:10.1002/jcb.30305 · Cited by 15 · see citing works

Discovery and biological evaluation of 1-{2,7-diazaspiro[3.5]nonan-2-yl}prop-2-en-1-one derivatives as covalent inhibitors of KRAS G12C with favorable metabolic stability and anti-tumor activity

Imaizumi, T., Akaiwa, M., Abe, T., Nigawara, T., Koike, T., Satake, Y., Watanabe, K., Kaneko, O., Amano, Y., Mori, K., et al. (2022) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2022.116949 · Cited by 14 · see citing works

Design of a Lead-Like Cysteine-Targeting Covalent Library and the Identification of Hits to Cys55 of Bfl-1

Lucas, S. C. C., Milbradt, A. G., Blackwell, J. H., Bonomo, S., Brierley, A., Cassar, D. J., Freeman, J., Hadfield, T. E., Morrill, L. A., Riemens, R., et al. (2024) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c00781 · Cited by 14 · see citing works

Discovery of Fulzerasib (GFH925) for the Treatment of KRAS G12C-Mutated Solid Tumors

Jiang, T., Lin, C., Le, S., Zhang, L., Liang, T., Cai, L., Lan, X., Ge, M., Liu, Z., He, W., et al. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c03183 · Cited by 13 · see citing works

High-throughput hit identification with acoustic ejection mass spectrometry

Wen, X., & McLaren, D. G. (2025) · SLAS TECHNOLOGY · doi:10.1016/j.slast.2025.100245 · Cited by 13 · see citing works

Design, synthesis, and evaluation of 4(1H)-quinolinone and urea derivatives as KRASG12C inhibitors with potent antitumor activity against KRAS-mutant non-small cell lung cancer

Cheng, R., Lv, X., Bu, H., Xu, Q., Wu, J., Xie, K., Tang, J., Wang, L., Zhuang, J., Zhang, Y., et al. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114808 · Cited by 13 · see citing works

A chemoproteomic platform for selective deubiquitinase inhibitor discovery

Cookson, R., Vuorinen, A., Pettinger, J., Kennedy, C. R., Kirkpatrick, J. M., Heap, R. E., Powell, A., Snijders, A. P., Skehel, M. J., House, D., et al. (2023) · Cell Reports Physical Science · doi:10.1016/j.xcrp.2023.101636 · Cited by 12 · see citing works

RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations

Bonsor, D. A., & Simanshu, D. K. (2023) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-062822-030450 · Cited by 13 · see citing works

Review of the impact of fragment-based drug design on PROTAC degrader discovery

Chen, P., Li, Q., & Lei, X. (2024) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2024.117539 · Cited by 12 · see citing works

Data processing for high-throughput mass spectrometry in drug discovery

Liu, C., & Zhang, H. (2024) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2024.2354871 · Cited by 10 · see citing works

Identification of Potential Inhibitors Targeting GTPase-Kirsten RAt Sarcoma Virus (K-Ras) Driven Cancers via E-Pharmacophore-Based Virtual Screening and Drug Repurposing Approach

Kumar, S. U., Varghese, R. P., Preethi, V. A., Doss, C. G. P., & Zayed, H. (2023) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2811288 · Cited by 10 · see citing works

Emerging opportunities for intact and native protein analysis using chemical proteomics

Edwards, A. N., & Hsu, K. (2024) · Analytica Chimica Acta · doi:10.1016/j.aca.2024.343551 · Cited by 11 · see citing works

Size-Dependent Target Engagement of Covalent Probes

Petri, L., Gabizon, R., Ferenczy, G. G., Péczka, N., Egyed, A., Ábrányi‐Balogh, P., Takács, T., & Keserű, G. M. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c00017 · Cited by 9 · see citing works

Covalent fragment mapping of KRasG12C revealed novel chemotypes with in vivo potency

Orgován, Z., Péczka, N., Petri, L., Ábrányi‐Balogh, P., Ranđelović, I., Tóth, S., Szakács, G., Nyíri, K., Vértessy, B. G., Pálfy, G., et al. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115212 · Cited by 10 · see citing works

Inhibitors of the GTPase KRASG12Cin cancer: a patent review (2019-2021)

Xu, Q., Zhang, G., Liu, Q., Li, S., & Zhang, Y. (2022) · Expert Opinion on Therapeutic Patents · doi:10.1080/13543776.2022.2032648 · Cited by 9 · see citing works

Covalent fragment libraries in drug discovery—Design, synthesis, and screening methods

Hocking, B. J. W., Armstrong, A., & Mann, D. J. (2023) · Progress in medicinal chemistry · doi:10.1016/bs.pmch.2023.10.003 · Cited by 9 · see citing works

Rapid Affinity and Microsomal Stability Ranking of Crude Mixture Libraries of Histone Deacetylase Inhibitors

Tyagarajan, S., Andrews, C. L., Beshore, D. C., Buevich, A. V., Curran, P. J., Dandliker, P. J., Greshock, T. J., Hoar, J. L., Kim, A. C., Karnachi, P., et al. (2024) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.4c00345 · Cited by 8 · see citing works

In Silico Evaluation of the Thr58-Associated Conserved Water with KRAS Switch-II Pocket Binders

Leini, R., & Pantsar, T. (2023) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.2c01479 · Cited by 8 · see citing works

A Photoaffinity‐Based Fragment‐Screening Platform for Efficient Identification of Protein Ligands

Grant, E. K., Fallon, D. J., Hann, M. M., Fantom, K. G. M., Quinn, C. J., Zappacosta, F., Annan, R. S., Chung, C., Bamborough, P., Dixon, D. P., et al. (2020) · Angewandte Chemie · doi:10.1002/ange.202008361 · Cited by 8 · see citing works

Nonclinical Safety Profile of Sotorasib, a KRAS G12C -Specific Covalent Inhibitor for the Treatment of KRAS p.G12C -Mutated Cancer

Ishida, K., Werner, J. A., Davies, R., Fan, F., Thomas, B., Wahlstrom, J. L., Lipford, J. R., & Monticello, T. M. (2021) · International Journal of Toxicology · doi:10.1177/10915818211022965 · Cited by 8 · see citing works

Sulfopin, a selective covalent inhibitor of Pin1, blocks Myc-driven tumor initiation and growth in vivoPreprint

Dubiella, C., Pinch, B. J., Zaidman, D., Manz, T. D., Poon, E., He, S., Resnick, E., Langer, E. M., Daniel, C. J., Seo, H., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.20.998443 · Cited by 8 · see citing works

Identification of an Allene Warhead That Selectively Targets a Histidine Residue in the Escherichia coli Oxidoreductase Enzyme DsbA

Tasdan, Y., Balaji, G. R., Akhtar, N., Ilyichova, O. V., Cunliffe, T., Heras, B., Strat, L. L., Murray, J. B., Capuano, B., Scanlon, M. J., et al. (2025) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5c00016 · Cited by 7 · see citing works

Binding modes of the KRAS(G12C) inhibitors GDC-6036 and LY3537982 revealed by all atom molecular dynamics simulations

Leini, R., Kapp, J. N., Kopra, K., & Pantsar, T. (2025) · Scientific Reports · doi:10.1038/s41598-025-07532-2 · Cited by 8 · see citing works

A practical method for determining the rate of covalent modification of fragments and leads

Jeon, J., Kholodar, S. A., Tran, B. H., Mallinger, K. E., Erlanson, D. A., & Everley, R. A. (2025) · Nature Communications · doi:10.1038/s41467-025-66924-0 · Cited by 7 · see citing works

A New Dawn for Targeted Cancer Therapy: Small Molecule Covalent Binding Inhibitor Targeting K-Ras (G12C)

Li, N., Liu, C., Zhang, W., & Rao, G. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673258913231019113814 · Cited by 7 · see citing works

Multiscale calculations reveal new insights into the reaction mechanism between KRAS G12C and α, β-unsaturated carbonyl of covalent inhibitors

Yan, X. H., Qu, C., Li, Q., Zhu, L., Tong, H. H. Y., Liu, H., Ouyang, Q., & Yao, X. (2024) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2024.03.027 · Cited by 7 · see citing works

Enhanced Declustering Enables Native Top-Down Analysis of Membrane Protein Complexes using Ion-Mobility Time-Aligned Fragmentation

Sokratous, K., Cooper-Shepherd, D. A., Ujma, J., Qu, F., Giles, K., Ben-Younis, A., Hensen, M., Langridge, J., Gault, J., Jazayeri, A., et al. (2024) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.4c00190 · Cited by 8 · see citing works

Structural insights, regulation, and recent advances of RAS inhibitors in the MAPK signaling cascade: a medicinal chemistry perspective

Prajapati, V., Singh, A. K., Kumar, A. M., Singh, H., Pathak, P., Grishina, M., Kumar, V., Khalilullah, H., Verma, A., & Kumar, P. (2025) · RSC Medicinal Chemistry · doi:10.1039/d4md00923a · Cited by 6 · see citing works

Targeting oncogenic KRasG13C with nucleotide-based covalent inhibitors

Goebel, L., Kirschner, T., Koska, S., Rai, A., Janning, P., Maffini, S., Vatheuer, H., Czodrowski, P., Goody, R. S., Müller, M. P., et al. (2023) · eLife · doi:10.7554/elife.82184 · Cited by 6 · see citing works

Normalizing Covalent Potency for Electrophilicity with Ligand Reactivity Efficiency

Horning, B. D., Kingston, C., Simon, G. M., Patricelli, M. P., Weinstein, D. S., & Cook, B. N. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c01803 · Cited by 7 · see citing works

Evolution of structure-guided drug design strategies targeting mutations in codon 12 of KRAS

Dorandish, S., Bhayekar, K., Singh, A., Kushwaha, N. D., Malin, E., Serafimovski, S., Kelm, J. M., Gavande, N. S., & Lakkaniga, N. R. (2025) · RSC Medicinal Chemistry · doi:10.1039/d5md00169b · Cited by 5 · see citing works

Fragment-based Drug Discovery Successful Contributions to Current Pharmacotherapeutic Agents Arsenal against Aggressive Cancers: A Mini-Review

Santos, L. M., & da Silveira, N. J. F. (2023) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/1871520623666230714163823 · Cited by 5 · see citing works

From Transient to Stable: Incorporating Electrophiles in Genetically-Encoded and DNA-Encoded Libraries of Peptide-Derived Macrocycles

Walker, J. C., Yan, K., & Derda, R. (2026) · Biochemistry · doi:10.1021/acs.biochem.5c00646 · Cited by 4 · see citing works

Expedited SARS‐CoV‐2 Main Protease Inhibitor Discovery through Modular ‘Direct‐to‐Biology’ Screening

Wilders, H., Biggs, G. S., Rowe, S. M., Cawood, E. E., Riziotis, I. G., Rendina, A. R., Grant, E. K., Pettinger, J., Fallon, D. J., Skehel, M. J., et al. (2024) · Angewandte Chemie · doi:10.1002/ange.202418314 · Cited by 3 · see citing works

Evolution of computational techniques against various KRAS mutants in search for therapeutic drugs: a review article

Mehmood, A., Hakami, M. A., Ogaly, H. A., Subramaniyan, V., Khalid, A., & Wadood, A. (2025) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-025-04767-8 · Cited by 3 · see citing works

Programmable synthesis of alkaloidal frameworks integrating Michael acceptor generates covalent probes for targeting POLE3 in HBV replication

Kaneko, N., Himeno, M., Kobayashi, Y., Tanifuji, R., Kubota, H., Mizoguchi, H., Muroi, M., Suzuki, T., Sugiyama, M., Dohmae, N., et al. (2025) · RSC Chemical Biology · doi:10.1039/d5cb00268k · Cited by 2 · see citing works

Application of Acoustic Ejection Mass Spectrometry to Accelerate Drug Discovery

Meng, J., Abucayon, E. G., Wleklinski, M., Li, S., & Liu, C. (2026) · Analysis & Sensing · doi:10.1002/anse.202500218 · Cited by 2 · see citing works

A Direct-to-Biology Amine–Acid Amination for Rapid Phenotypic Profiling of Lysosomotropic Natural Products

Kao, Y.-T., Abdelalim, M., Mauro, C., Douthwaite, J. L., McGrath, A., Meyer, S. R., Singha, S., Diaz, D. F., Wang, M., Wang, S., et al. (2026) · Journal of the American Chemical Society · doi:10.1021/jacs.6c06623 · Cited by 2 · see citing works

The future of covalent inhibition

Keserű, G. M., & Erlanson, D. A. (2020) · Annual reports in medicinal chemistry · doi:10.1016/bs.armc.2020.10.003 · Cited by 1 · see citing works

LUMAKRAS® (sotorasib)

Tamayo, N. A., Wurz, R. P., & Lanman, B. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21861-3.00001-2 · Cited by 1 · see citing works

Drug discovery technologies–Current and future trends

Noe, M. C., Steppan, C. M., & Weston, A. D. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-29808-0.00019-4 · Cited by 1 · see citing works

Advancing label-free screening technologies to enhance drug discovery efficiency

Cheng, R., & Liu, C. (2026) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2026.2622372 · Cited by 1 · see citing works

GalaxyCDock: Webserver for Covalent Protein–Ligand Binding Mode Prediction

Lee, S., Jung, N., Woo, H., Yang, J., & Seok, C. (2026) · Journal of Molecular Biology · doi:10.1016/j.jmb.2026.169807 · Cited by 1 · see citing works

Accelerate Your Science: Direct-to-Biology Strategies in Medicinal Chemistry

Hiesinger, K., & Knapp, S. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00996 · Cited by 1 · see citing works

PhotoAffinity Bits: A Photoaffinity-Based Fragment Screening Platform for Efficient Identification of Protein LigandsPreprint

Grant, E. K., Fallon, D. J., Hann, M. M., Fantom, K. G. M., Quinn, C. J., Zappacosta, F., Annan, R. S., Chung, C., Bamborough, P., Dixon, D. P., et al. (2020) · ChemRxiv · doi:10.26434/chemrxiv.12053445.v1 · Cited by 1 · see citing works

Sotorasib (LUMAKRAS), An Irreversible Covalent Inhibitor of KRAS G12C

Lanman, B. A., & Parsons, A. T. (2022) · doi:10.1002/9781119847281.ch10

A chemoproteomic platform for reactive fragment profiling against the deubiquitinasesPreprint

Cookson, R., Vuorinen, A., Pettinger, J., Kennedy, C. R., Kirkpatrick, J. M., Heap, R. E., Powell, A. J., Snijders, A. P., Skehel, M. J., House, D., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.01.526632

KRAS Inhibitors

Corey, E. J., & Wu, Y. (2023) · doi:10.1002/9781394207145.ch21

Abstract IA20: Unlocked groove—developing covalent inhibitors of KRASG12C

Lipford, J. R., Cee, V. J., Lanman, B. A., Saiki, A. Y., Rex, K. L., Volak, L. P., Shimanovich, R., & Hinkle, B. (2020) · Molecular Cancer Research · doi:10.1158/1557-3125.ras18-ia20

Abstract 929: Discovery of novel covalent KRASG12C inhibitors that display high potency and selectivity in vitro and in vivo

Li, L., Janes, M. R., Zhang, J., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Feng, J., et al. (2018) · Cancer Research · doi:10.1158/1538-7445.am2018-929

Computer-aided drug design of some KRAS G12C inhibitors: Targeting the covalent and allosteric binding site for cancer therapy

Ogunlana, A. T., Oyedele, A.-Q. K., Boyenle, I. D., Ayoola, S. O., Ajibare, A. C., Adeyemi, A. O., Jinadu, L. A., Oluwafemi, A. T., Alausa, A. O., & Adelusi, T. I. (2022) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2022.101032 · Cited by 19 · see citing works

Discovery of tetrahydropyridopyrimidines as irreversible covalent inhibitors of KRAS-G12C with in vivo activity

Fell, J. B., Fischer, J. P., Baer, B. R., Ballard, J., Blake, J. F., Bouhana, K., Brandhuber, B. J., Briere, D. M., Burgess, L. E., Burkard, M. R., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00382 · Cited by 120 · see citing works

Discovery and characterization of ABSK071, a novel and potent small-molecule covalent inhibitor for KRAS-G12C

Guo, F., Zhao, Y., Yu, H., Xu, Y., Chen, Z., & Yang, S. (2022) · European Journal of Cancer · doi:10.1016/s0959-8049(22)00863-2