Cited by 112Protein Degradation and InhibitorsChemical Synthesis and AnalysisMelanoma and MAPK Pathways

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Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC

Yang, Fang, Wen, Yalei, Wang, Chaofan, Zhou, Yuee, Zhou, Yang, Zhang, Zhi-Min, Liu, Tongzheng, Lu, Xiaoyun·2022·European Journal of Medicinal Chemistry

DOI 10.1016/j.ejmech.2021.114088

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Abstract

KRAS is the most frequently mutated oncogene and plays a predominant role in driving initiation and progression of multiple cancers. Attempts to degrade the oncogene KRAS G12C with PROTAC strategy have been considered as an alternative strategy to combate cancers. However, the irreversible PROTACs may compromise the substoichiometric activity to decrease the potency. Herein, we report the development of YF135, the first reversible-covalent PROTAC capable of recruiting VHL mediated proteasomal degradation of KRAS G12C. YF135 induces the rapid and sustained degradation of endogenous KRAS G12C and attenuates pERK signaling in H358 and H23 cells in a reversible manner.

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Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
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
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
RAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
The Ras-RasGAP Complex: Structural Basis for GTPase Activation and Its Loss in Oncogenic Ras Mutants
Scheffzek, K., Ahmadian, M. R., Kabsch, W., Wiesmüller, L., Lautwein, A., Schmitz, F., & Wittinghofer, A. (1997) · Science · doi:10.1126/science.277.5324.333 · Cited by 1,543
Induced protein degradation: an emerging drug discovery paradigm
Lai, A. C., & Crews, C. M. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.211 · Cited by 1,486
Catalytic in vivo protein knockdown by small-molecule PROTACs
Bondeson, D. P., Mares, A., Smith, I. E. D., Ko, E., Campos, S., Miah, A. H., Mulholland, K. E., Routly, N., Buckley, D. L., Gustafson, J. L., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1858 · Cited by 1,356
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
Acquired Resistance to KRAS G12C Inhibition in Cancer
Awad, M. M., Liu, S., Rybkin, I. I., Arbour, K. C., Dilly, J., Zhu, V. W., Johnson, M. L., Heist, R. S., Patil, T., Riely, G. J., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2105281 · Cited by 1,247
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

Show all 38 references

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BindingDB Entry 50021193: Emerging and Re-emerging Warheads for Targeted Covalent Inhibitors: An Update.
BindingDB (2025) · UC San Diego · doi:10.7270/q2vm4hvh

Authors: Yang, F., Wen, Y., Wang, C., Zhou, Y., Zhou, Y., Zhang, Z.-M., Liu, T., & Lu, X.
Affiliations: Jinan University (CN)
Corresponding author: Liu, Tongzheng
Lu, Xiaoyun
ORCID: Yang, Fang
Wen, Yalei
Wang, Chaofan
Zhou, Yuee
Zhou, Yang
Liu, Tongzheng
Lu, Xiaoyun
Venue: European Journal of Medicinal Chemistry
Publisher: Elsevier BV
Published: 2022-02
Volume: 230
Pages: 114088
ISSN: 0223-5234 (ISSN-L)
DOI: 10.1016/j.ejmech.2021.114088
OpenAlex: W4206601451
Cited by: 109
References: 38
Citations by year: 2026: 16 · 2025: 29 · 2024: 27 · 2023: 21 · 2022: 15
FWCI: 7.83
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: European Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords: KRAS G12C, PROTACs, VHL, proteasomal degradation, PERK signaling, H358 cells, H23 cells, KRAS inhibitors
MeSH terms: Humans, Mutation, Neoplasms, Oligopeptides, Oncogenes, Proto-Oncogene Proteins p21(ras), Carcinogenesis

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Efficient targeted oncogenic KRASG12C degradation via first reversible-covalent PROTAC

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