Discovery of the First-in-Class Agonist-Based SOS1 PROTACs Effective in Human Cancer Cells Harboring Various KRAS Mutations

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

Drugging the undruggable RAS: Mission Possible?

Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works

KRAS ^G12C Inhibition with Sotorasib in Advanced Solid Tumors

Hong, D. S., Fakih, M. G., Strickler, J. H., Desai, J., Durm, G. A., Shapiro, G. I., Falchook, G. S., Price, T. J., Sacher, A., Denlinger, C. S., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1917239 · Cited by 1,733 · 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

Structural basis of PROTAC cooperative recognition for selective protein degradation

Gadd, M. S., Testa, A., Lucas, X., Chan, K.-H., Chen, W., Lamont, D. J., Zengerle, M., & Ciulli, A. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2329 · Cited by 1,242 · 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

PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer

Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521738113 · Cited by 852 · see citing works

Ras superfamily GEFs and GAPs: validated and tractable targets for cancer therapy?

Vigil, D., Cherfils, J., Rossman, K. L., & Der, C. J. (2010) · Nature reviews. Cancer · doi:10.1038/nrc2960 · Cited by 816 · see citing works

A selective BCL-XL PROTAC degrader achieves safe and potent antitumor activity

Khan, S., Zhang, X., Lv, D., Zhang, Q., He, Y., Zhang, P., Liu, X., Thummuri, D., Yuan, Y., Wiegand, J. S., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0668-z · Cited by 688 · see citing works

Targeted protein degradation: elements of PROTAC design

Paiva, S.-L., & Crews, C. M. (2019) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2019.02.022 · Cited by 586 · see citing works

PROTACs: An Emerging Therapeutic Modality in Precision Medicine

Nalawansha, D. A., & Crews, C. M. (2020) · Cell chemical biology · doi:10.1016/j.chembiol.2020.07.020 · Cited by 514 · 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

BI-3406, a Potent and Selective SOS1–KRAS Interaction Inhibitor, Is Effective in KRAS-Driven Cancers through Combined MEK Inhibition

Hofmann, M. H., Gmachl, M., Ramharter, J., Savarese, F., Gerlach, D., Marszalek, J. R., Sanderson, M. P., Kessler, D., Trapani, F., Arnhof, H., et al. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-20-0142 · Cited by 444 · see citing works

Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS–SOS1 interaction

Hillig, R. C., Sautier, B., Schroeder, J., Moosmayer, D., Hilpmann, A., Stegmann, C. M., Werbeck, N. D., Briem, H., Boemer, U., Weiske, J., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1812963116 · Cited by 388 · see citing works

SPR-measured dissociation kinetics of PROTAC ternary complexes influence target degradation rate

Roy, M. J., Winkler, S., Hughes, S. J., Whitworth, C., Galant, M., Farnaby, W., Rumpel, K., & Ciulli, A. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.9b00092 · Cited by 386 · see citing works

Approach for targeting Ras with small molecules that activate SOS-mediated nucleotide exchange

Burns, M. C., Sun, Q., Daniels, R. N., Camper, D., Kennedy, J. P., Phan, J., Olejniczak, E. T., Lee, T., Waterson, A. G., Rossanese, O. W., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315798111 · Cited by 199 · see citing works

Sos-mediated cross-activation of wild-type Ras by oncogenic Ras is essential for tumorigenesis

Jeng, H., Taylor, L. J., & Bar‐Sagi, D. (2012) · Nature Communications · doi:10.1038/ncomms2173 · Cited by 176 · see citing works

Discovery of SHP2-D26 as a First, Potent, and Effective PROTAC Degrader of SHP2 Protein

Wang, M., Lu, J., Wang, M., Yang, C.-Y., & Wang, S. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00471 · Cited by 172 · see citing works

A Ras-induced conformational switch in the Ras activator Son of sevenless

Freedman, T. S., Sondermann, H., Friedland, G. D., Kortemme, T., Bar‐Sagi, D., Marqusee, S., & Kuriyan, J. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608127103 · Cited by 160 · see citing works

Structure-based Mutagenesis Reveals Distinct Functions for Ras Switch 1 and Switch 2 in Sos-catalyzed Guanine Nucleotide Exchange

Hall, B. E., Yang, S. S., Boriack‐Sjodin, P. A., Kuriyan, J., & Bar‐Sagi, D. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m101727200 · Cited by 132 · see citing works

SOS GEFs in health and disease

Baltanás, F. C., Zarich, N., Rojas-Cabañeros, J. M., & Santos, E. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188445 · Cited by 100 · see citing works

RasGRP1 opposes proliferative EGFR–SOS1–Ras signals and restricts intestinal epithelial cell growth

Depeille, P., Henricks, L. M., van de Ven, R. A. H., Lemmens, E., Wang, C.-Y., Matli, M., Werb, Z., Haigis, K. M., Donner, D., Warren, R., et al. (2015) · Nature Cell Biology · doi:10.1038/ncb3175 · Cited by 80 · see citing works

One Atom Makes All the Difference: Getting a Foot in the Door between SOS1 and KRAS

Ramharter, J., Kessler, D., Ettmayer, P., Hofmann, M. H., Gerstberger, T., Gmachl, M., Wunberg, T., Kofink, C. C., Sanderson, M. P., Arnhof, H., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01949 · Cited by 73 · see citing works

Drugging the Undruggable: Advances on RAS Targeting in Cancer

Molina‐Arcas, M., Samani, A., & Downward, J. (2021) · Genes · doi:10.3390/genes12060899 · Cited by 73 · see citing works

Discovery and Structure-Based Optimization of Benzimidazole-Derived Activators of SOS1-Mediated Nucleotide Exchange on RAS

Hodges, T. R., Abbott, J. R., Little, A. J., Sarkar, D., Salovich, J. M., Howes, J. E., Akan, D. T., Sai, J., Arnold, A. L., Browning, C. F., et al. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01108 · Cited by 62 · see citing works

Unique dependence on Sos1 in KrasG12D-induced leukemogenesis

You, X., Kong, G., Ranheim, E. A., et al. (2018) · Blood · doi:10.1182/blood-2018-09-874107 · Cited by 40 · see citing works

Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS

Abbott, J. R., Patel, P. A., Howes, J. E., Akan, D. T., Kennedy, J. P., Burns, M. C., Browning, C. F., Sun, Q., Rossanese, O. W., Phan, J., et al. (2018) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.8b00296 · Cited by 35 · see citing works

Discovery of Sulfonamide-Derived Agonists of SOS1-Mediated Nucleotide Exchange on RAS Using Fragment-Based Methods

Sarkar, D., Olejniczak, E. T., Phan, J., Coker, J. A., Sai, J., Arnold, A. L., Beesetty, Y., Waterson, A. G., & Fesik, S. W. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00511 · Cited by 33 · see citing works

Development of Agonist-Based PROTACs Targeting Liver X Receptor

Xu, H., Ohoka, N., Yokoo, H., Nemoto, K., Ohtsuki, T., Matsufuji, H., Naito, M., Inoué, T., Tsuji, G., & Demizu, Y. (2021) · Frontiers in Chemistry · doi:10.3389/fchem.2021.674967 · Cited by 23 · see citing works

Small Molecule SOS1 Agonists Modulate MAPK and PI3K Signaling via Independent Cellular Responses

Akan, D. T., Howes, J. E., Sai, J., Arnold, A. L., Beesetty, Y., Phan, J., Olejniczak, E. T., Waterson, A. G., & Fesik, S. W. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b00869 · Cited by 22 · 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

BRAF — a tumour-agnostic drug target with lineage-specific dependencies

Hanrahan, A. J., Chen, Z., Rosen, N., & Solit, D. B. (2024) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00852-0 · Cited by 136 · see citing works

PROTAC therapy as a new targeted therapy for lung cancer

Li, J. W., Zheng, G., Kaye, F. J., & Wu, L. (2023) · Molecular Therapy · doi:10.1016/j.ymthe.2022.11.011 · Cited by 87 · see citing works

Assessing the significance of KRAS G12C mutation: Clinicopathologic features, treatments, and survival outcomes in a real-world KRAS mutant non-small cell lung cancer cohort.

Cui, W., Franchini, F., Alexander, M., Officer, A., Wong, H., IJzerman, M. J., Desai, J., & Solomon, B. (2020) · Journal of Clinical Oncology · doi:10.1200/jco.2020.38.15_suppl.e19324 · Cited by 3 · see citing works

127P RAS, RAF and NF1 oncogenic mutations in KRAS-mutated lung adenocarcinoma

Marinelli, D., Pisegna, S., Chiavassa, A., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.09.128

Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

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Molecular profile of KRAS G12C-mutant colorectal and non-small-cell lung cancer

Araujo, L. H., Souza, B. M., Leite, L. R., Parma, S. A. F., Lopes, N. P., Malta, F. S. V., & Freire, M. C. M. (2021) · BMC Cancer · doi:10.1186/s12885-021-07884-8 · Cited by 41 · see citing works

KRAS gene amplification to define a distinct molecular subgroup of gastroesophageal adenocarcinoma.

Xu, D., Alpert, L., Xu, P., Tumuluru, S., Kanteti, R., Henderson, L., O’Day, E., Cecchi, F., Blackler, A. R., Liao, W., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.4065