The Research Progress of Direct KRAS G12C Mutation Inhibitors

Improved Overall Survival in Melanoma with Combined Dabrafenib and Trametinib

Robert, C., Karaszewska, B., Schachter, J., Rutkowski, P. L., Mackiewicz, A. A., Stroyakovskiy, D., Lichinitser, M., Dummer, R., Grange, F., Mortier, L., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1412690 · Cited by 2,698 · see citing works

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

Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · see citing works

The Clinical KRAS(G12C) Inhibitor AMG 510 Drives Anti-Tumour Immunity

Canon, J., Rex, K., Saiki, A. Y., Mohr, C., Cooke, K., Bagal, D., Gaida, K., Holt, T., Knutson, C. G., Koppada, N., et al. (2019) · Nature · doi:10.1038/s41586-019-1694-1 · Cited by 2,277 · see citing works

A Comprehensive Survey of Ras Mutations in Cancer

Prior, I. A., Lewis, P. D., & Mattos, C. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-2612 · Cited by 2,063 · see citing works

The KRASG12C Inhibitor MRTX849 Provides Insight toward Therapeutic Susceptibility of KRAS-Mutant Cancers in Mouse Models and Patients

Hallin, J., Engstrom, L. D., Hargis, L., Calinisan, A., Aranda, R., Briere, D. M., Sudhakar, N., Bowcut, V., Baer, B. R., Ballard, J. A., et al. (2020) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-1167 · Cited by 1,304 · see citing works

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 · cited 1× · see citing works

RAS isoforms and mutations in cancer at a glance

Hobbs, G. A., Der, C. J., & Rossman, K. L. (2016) · Journal of Cell Science · doi:10.1242/jcs.182873 · Cited by 973 · 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

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

Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759 · see citing works

Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism

Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N. (2016) · Science · doi:10.1126/science.aad6204 · Cited by 691 · see citing works

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

Ostrem, J. M. L., & Shokat, K. M. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.139 · Cited by 641 · see citing works

Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition

Xue, J. Y., Zhao, Y., Aronowitz, J., Mai, T. T., Vides, A., Qeriqi, B., Kim, D., Li, C., de Stanchina, E., Mazutis, L., et al. (2020) · Nature · doi:10.1038/s41586-019-1884-x · Cited by 543 · see citing works

Drugging an undruggable pocket on KRAS

Kessler, D., Gmachl, M., Mantoulidis, A., Martin, L. J., Zoephel, A., Mayer, M., Gollner, A., Covini, D., Fischer, S., Gerstberger, T., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1904529116 · Cited by 449 · see citing works

Rational Selection of Syngeneic Preclinical Tumor Models for Immunotherapeutic Drug Discovery

Mosely, S. I. S., Prime, J. E., Sainson, R. C. A., Koopmann, J., Wang, D. Y. Q., Greenawalt, D. M., Ahdesmaki, M. J., Leyland, R., Mullins, S., Pacelli, L., et al. (2016) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-16-0114 · Cited by 410 · 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

Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor

Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M., Hunter, J., Kim, N. D., Xie, T., et al. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201307387 · Cited by 300 · see citing works

Preclinical Development of Ipilimumab and Nivolumab Combination Immunotherapy: Mouse Tumor Models, In Vitro Functional Studies, and Cynomolgus Macaque Toxicology

Selby, M., Engelhardt, J., Johnston, R. J., Lu, L.-S., Han, M., Thudium, K. B., Yao, D., Quigley, M. M., Valle, J., Wang, C., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161779 · Cited by 230 · see citing works

Development of combination therapies to maximize the impact of KRAS-G12C inhibitors in lung cancer

Molina-Arcas, M., Moore, C., Rana, S., van Maldegem, F., Mugarza, E., Romero-Clavijo, P., Herbert, E., Horswell, S., Li, L.-S., Janes, M. R., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw7999 · Cited by 203 · see citing works

KRAS G12C Game of Thrones, which direct KRAS inhibitor will claim the iron throne?

Nagasaka, M., Li, Y., Sukari, A., Ou, S.-H. I., Al-Hallak, M. N., & Azmi, A. S. (2020) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2020.101974 · Cited by 185 · see citing works

Phase 1 study evaluating the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 510, a novel small molecule <i>KRAS^G12C</i> inhibitor, in advanced solid tumors.

Fakih, M., O'Neil, B., Price, T. J., Falchook, G. S., Desai, J., Kuo, J., Govindan, R., Rasmussen, E., Morrow, P. K. H., Ngang, J., et al. (2019) · Journal of Clinical Oncology · doi:10.1200/jco.2019.37.15_suppl.3003 · Cited by 172 · see citing works

Structure-based development of new RAS-effector inhibitors from a combination of active and inactive RAS-binding compounds

Cruz-Migoni, A., Canning, P., Quevedo, C. E., Bataille, C. J. R., Béry, N., Miller, A., Russell, A. J., Phillips, S. E. V., Carr, S. B., & Rabbitts, T. H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1811360116 · Cited by 135 · see citing works

Small molecule inhibitors of RAS-effector protein interactions derived using an intracellular antibody fragment

Quevedo, C. E., Cruz-Migoni, A., Béry, N., Miller, A., Tanaka, T. U., Petch, D., Bataille, C. J. R., Lee, L. Y. W., Fallon, P. S., Tulmin, H., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05707-2 · Cited by 132 · see citing works

Ras Binder Induces a Modified Switch-II Pocket in GTP and GDP States

Gentile, D. R., Rathinaswamy, M. K., Jenkins, M. L., Moss, S. M., Siempelkamp, B. D., Renslo, A. R., Burke, J. E., & Shokat, K. M. (2017) · Cell chemical biology · doi:10.1016/j.chembiol.2017.08.025 · Cited by 116 · see citing works

Affinity Profiling of the Cellular Kinome for the Nucleotide Cofactors ATP, ADP, and GTP

Becher, I., Savitski, M. M., Savitski, M. F., Hopf, C., Bantscheff, M., & Drewes, G. (2012) · ACS Chemical Biology · doi:10.1021/cb3005879 · Cited by 96 · see citing works

A bright future for KRAS inhibitors

Bar-Sagi, D., Knelson, E. H., & Sequist, L. V. (2020) · Nature Cancer · doi:10.1038/s43018-019-0016-8 · Cited by 74 · see citing works

KRAS: Reasons for optimism in lung cancer

Lindsay, C. R., Jamal‐Hanjani, M., Forster, M. D., & Blackhall, F. H. (2018) · European Journal of Cancer · doi:10.1016/j.ejca.2018.05.001 · Cited by 52 · see citing works

High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling

Burns, M. C., Howes, J. E., Sun, Q., Little, A. J., Camper, D. V., Abbott, J. R., Phan, J., Lee, T., Waterson, A. G., Rossanese, O. W., et al. (2018) · Analytical Biochemistry · doi:10.1016/j.ab.2018.01.025 · Cited by 50 · see citing works

Phase I study of AMG 510, a novel molecule targeting KRAS G12C mutant solid tumours

Govindan, R., Fakih, M. G., Price, T. J., Falchook, G. S., Desai, J., Kuo, J. C., Strickler, J. H., Krauss, J. C., Li, B. T., Denlinger, C. S., et al. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz244.008 · Cited by 40 · see citing works

Identification of a new inhibitor of KRAS‐PDEδ interaction targeting KRAS mutant nonsmall cell lung cancer

Leung, E. L., Luo, L. X., Li, Y., Liu, Z., Li, L. L., Shi, D. F., Xie, Y., Huang, M., Lu, L. L., Duan, F. G., et al. (2019) · International Journal of Cancer · doi:10.1002/ijc.32222 · Cited by 39 · see citing works

Therapeutic Targeting of Oncogenic K‐Ras by a Covalent Catalytic Site Inhibitor

Lim, S. M., Westover, K. D., Ficarro, S. B., Harrison, R. A., Choi, H. G., Pacold, M. E., Carrasco, M. A., Hunter, J., Kim, N. D., Xie, T., et al. (2013) · Angewandte Chemie · doi:10.1002/ange.201307387 · Cited by 31 · see citing works

Small molecule combats cancer-causing KRAS protein at last

Herbst, R. S., & Schlessinger, J. (2019) · Nature · doi:10.1038/d41586-019-03242-8 · Cited by 23 · see citing works

Abstract 4484: Discovery and in vitro characterization of AMG 510–a potent and selective covalent small-molecule inhibitor of KRASG12C

Saiki, A. Y., Gaida, K., Rex, K. L., Achanta, P., Miguel, T. S., Koppada, N., Bagal, D., Lanman, B. A., Foti, R., McCarter, J. D., et al. (2019) · Cancer Research · doi:10.1158/1538-7445.am2019-4484 · Cited by 15 · see citing works

Selective apoptosis-inducing activity of synthetic hydrocarbon-stapled SOS1 helix with d-amino acids in H358 cancer cells expressing KRASG12C

Xu, L., Li, C., An, L.-Y., Dai, Z., Chen, X., You, Q., Hu, C., & Di, B. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.111844 · Cited by 15 · see citing works

Putting the brakes on KRAS-G12C nucleotide cycling

Shipman, L. (2016) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.40 · Cited by 7 · 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

Targeting the undruggable oncogenic KRAS: the dawn of hope

Asimgil, H., Ertetik, U., Çevik, N. C., Ekizce, M., Doğruöz, A., Gökalp, M., Sever, E. A., Istvánffy, R., Friess, H., Ceyhan, G. O., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.153688 · Cited by 55 · see citing works

Genetic differences between smokers and never-smokers with lung cancer

Kuśnierczyk, P. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1063716 · Cited by 45 · 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 36 · see citing works

Potential biomarkers uncovered by bioinformatics analysis in sotorasib resistant-pancreatic ductal adenocarcinoma

Ramalingam, P. S., Priyadharshini, A., Emerson, I. A., & Arumugam, S. (2023) · Frontiers in Medicine · doi:10.3389/fmed.2023.1107128 · Cited by 25 · see citing works

Multiple cancers escape from multiple MAPK pathway inhibitors and use DNA replication stress signaling to tolerate aberrant cell cycles

Hoffman, T. E., Nangia, V., Ill, C. R., Passanisi, V. J., Armstrong, C., Yang, C., & Spencer, S. L. (2023) · Science Signaling · doi:10.1126/scisignal.ade8744 · Cited by 22 · see citing works

Computational design and validation of effective siRNAs to silence oncogenic KRAS

Ramalingam, P. S., & Arumugam, S. (2023) · 3 Biotech · doi:10.1007/s13205-023-03767-w · Cited by 16 · see citing works

A pharmacological exploration of targeted drug therapy in non-small cell lung cancer

Jayan, A. P., Anandu, K. R., Madhu, K., & Nirmala, S. V. (2022) · Medical Oncology · doi:10.1007/s12032-022-01744-6 · Cited by 16 · see citing works

Targeting Ras with protein engineering

Tomazini, A., & Shifman, J. M. (2023) · Oncotarget · doi:10.18632/oncotarget.28469 · Cited by 13 · see citing works

Synthetic Vulnerabilities in the KRAS Pathway

Román, M., Hwang, E. E., & Sweet-Cordero, A. (2022) · Cancers · doi:10.3390/cancers14122837 · Cited by 12 · see citing works

Research progress on small molecule inhibitors targeting KRAS G12C with acrylamide structure and the strategies for solving KRAS inhibitor resistance

Jiang, Z., Li, Y., Zhou, X., Wen, J., Zheng, P., & Zhu, W. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117627 · Cited by 9 · see citing works

Jorunnamycin A induces apoptosis in pancreatic ductal adenocarcinoma cells, spheroids, and patient-derived organoids by modulating KRAS-mediated survival pathways

Khine, H. E. E., Suriya, U., Rungrotmongkol, T., Chamni, S., Lu, Y., Bénard, A., Lan, B., Mukhopadhyay, D., Chang, D. K.-F., Biankin, A. V., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-95766-5 · Cited by 6 · see citing works

Evaluation of AMG510 Therapy on KRAS-Mutant Non–Small Cell Lung Cancer and Colorectal Cancer Cell Using a 3D Invasive Tumor Spheroid System under Normoxia and Hypoxia

Huang, M., Hou, W., Zhang, J., Li, M., Zhang, Z., Li, X., Chen, Z., Wang, C., & Yang, L. (2022) · Bioengineering · doi:10.3390/bioengineering9120792 · Cited by 6 · see citing works

A Nucleoside Analogue Featuring a C3′-Stereogenic All-Carbon Quaternary Center as a Bioenergetic Disruptor of KRAS-Mutated Pancreatic Cancer Cells

Tantawi, H. N., Mochirian, P., Truong, M., Beauregard, J., Collins, L., Kanaan, G. N., Komati, H., Leblanc, L., Maharsy, W. M., Manchoju, A., et al. (2025) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5c00378

BindingDB Entry 50021330: Research progress on small molecule inhibitors targeting KRAS G12C with acrylamide structure and the strategies for solving KRAS inhibitor resistance.

BindingDB (2025) · UC San Diego · doi:10.7270/q26d5znm

Multiple medicinal chemistry strategies of targeting KRAS: State-of-the art and future directions

Shang, Y., Fu, S., Hao, Q., Ying, H., Wang, J., & Shen, T. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2023.107092 · Cited by 17 · 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

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 127 · see citing works

Abstract 3237: Development of direct inhibitors of KRAS mutants for the treatment of cancer

Tian, X., Geng, G., & Wu, J. H. (2017) · Cancer Research · doi:10.1158/1538-7445.am2017-3237 · Cited by 1 · see citing works

Research progress on small molecule inhibitors targeting KRAS G12C with acrylamide structure and the strategies for solving KRAS inhibitor resistance

Jiang, Z., Li, Y., Zhou, X., Wen, J., Zheng, P., & Zhu, W. (2024) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2024.117627 · Cited by 9 · see citing works