Cited by 201Protein Degradation and InhibitorsChemical Synthesis and AnalysisUbiquitin and proteasome pathways

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Simple Structural Modifications Converting a Bona fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders

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Yang, Jiuling, Li, Yangbing, Aguilar, Angelo, Liu, Zhaomin, Yang, Chao-Yie, Wang, Shaomeng·2019·Journal of Medicinal Chemistry

DOI 10.1021/acs.jmedchem.9b00846PMC PMC7354697

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Abstract

Inducing protein degradation by proteolysis targeting chimeras (PROTACs) has gained tremendous momentum for its promise to discover and develop new therapies. Based upon our previously reported PROTAC MDM2 degraders, we have designed and synthesized additional analogues. Surprisingly, we found that simple structural modifications of MD-222, a bona fide MDM2 PROTAC degrader, converts it into a “molecular glue”, as exemplified by MG-277 . MG-277 induces only moderate MDM2 degradation and fails to activate wild-type p53 but is highly potent in inhibition of tumor cell growth in a p53-independent manner. Our mechanistic investigation established that MG-277 is not a PROTAC MDM2 degrader but instead works as a molecular glue, inducing degradation of a translation termination factor, GSPT1 to achieve its potent anticancer activity. Our study provides the first example that simple structural modifications can convert a bona fide PROTAC degrader into a molecular glue compound, which has a completely different mechanism of action.

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Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,397
Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems
Darden, T., York, D., & Pedersen, L. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464397 · Cited by 29,638
Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes
Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. C. (1977) · Journal of Computational Physics · doi:10.1016/0021-9991(77)90098-5 · Cited by 21,430
Protacs: Chimeric molecules that target proteins to the Skp1–Cullin–F box complex for ubiquitination and degradation
Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141230798 · Cited by 2,609
Identification of a Primary Target of Thalidomide Teratogenicity
Ito, T., Ando, H., Suzuki, T., Ogura, T., Hotta, K., Imamura, Y., Yamaguchi, Y., & Handa, H. (2010) · Science · doi:10.1126/science.1177319 · Cited by 2,136
Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells
Krönke, J., Udeshi, N. D., Narla, A., Grauman, P., Hurst, S. N., McConkey, M., Svinkina, T., Heckl, D., Comer, E., Li, X., et al. (2014) · Science · doi:10.1126/science.1244851 · Cited by 1,879
Phthalimide conjugation as a strategy for in vivo target protein degradation
Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E. (2015) · Science · doi:10.1126/science.aab1433 · Cited by 1,760
The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins
Lu, G., Middleton, R. E., Sun, H., Naniong, M., Ott, C. J., Mitsiades, C. S., Wong, K.-K., Bradner, J. E., & Kaelin, W. G. (2014) · Science · doi:10.1126/science.1244917 · Cited by 1,583
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

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Zhang, W., Li, S., Yao, Y., Mao, Y., Jiang, W., & Li, S. (2026) · Pharmacological Research · doi:10.1016/j.phrs.2026.109664
BindingDB Entry 50019244: Targeting the Epidermal Growth Factor Receptor with Molecular Degraders: State-of-the-Art and Future Opportunities.
BindingDB (2024) · UC San Diego · doi:10.7270/q26d5zbk
BindingDB Entry 50022933: Discovery of a Potent and Selective GSPT1 Molecular Glue Degrader for the Treatment of Castration-Resistant Prostate Cancer.
BindingDB (2026) · UC San Diego · doi:10.7270/q270869b
BindingDB Entry 50023352: Structure-Guided Design of ISOX-DUAL-Based Degraders Targeting BRD4 and CBP/EP300: A Case of Degrader Collapse.
BindingDB (2026) · UC San Diego · doi:10.7270/q2zg6z4s
BindingDB Entry 50018659: Developments of CRBN-based PROTACs as potential therapeutic agents.
BindingDB (2024) · UC San Diego · doi:10.7270/q27948wc
BindingDB Entry 50023760: Rational Design of Dual Degraders by Incorporating Molecular Glue Structural Features into PROTAC Degraders.
BindingDB (2026) · UC San Diego · doi:10.7270/q27086c7
BindingDB Entry 50016839: VHL-based PROTACs as potential therapeutic agents: Recent progress and perspectives.
BindingDB (2023) · UC San Diego · doi:10.7270/q2vm4h9b
BindingDB Entry 50019498: Design, synthesis, and biological evaluation of Wee1 kinase degraders.
BindingDB (2024) · UC San Diego · doi:10.7270/q2zw1r9s
BindingDB Entry 50020994: Facilitating the development of molecular glues: Opportunities from serendipity and rational design.
BindingDB (2025) · UC San Diego · doi:10.7270/q21v5kjn
BindingDB Entry 50014421: Development of MDM2 degraders based on ligands derived from Ugi reactions: Lessons and discoveries.
BindingDB (2022) · UC San Diego · doi:10.7270/q2rb78fp
BindingDB Entry 50022865: Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα).
BindingDB (2026) · UC San Diego · doi:10.7270/q2c2529g
BindingDB Entry 50023421: TBA
BindingDB (2026) · UC San Diego · doi:10.7270/q2f76jg7
BindingDB Entry 50018045: Natural Product-Inspired Targeted Protein Degraders: Advances and Perspectives.
BindingDB (2023) · UC San Diego · doi:10.7270/q2pv6qh4
BindingDB Entry 50012120: Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders.
BindingDB (2022) · UC San Diego · doi:10.7270/q2ks6w6j
BindingDB Entry 50020357: Unlocking DCAFs To Catalyze Degrader Development: An Arena for Innovative Approaches.
BindingDB (2024) · UC San Diego · doi:10.7270/q2vq374f
BindingDB Entry 50022023: Application and challenges of nitrogen heterocycles in PROTAC linker.
BindingDB (2025) · UC San Diego · doi:10.7270/q2kp86vh
BindingDB Entry 50015392: Development of Potent and Selective Janus Kinase 2/3 Directing PG-PROTACs.
BindingDB (2023) · UC San Diego · doi:10.7270/q2d79gbf
BindingDB Entry 50018350: Recent advances in epigenetic proteolysis targeting chimeras (Epi-PROTACs).
BindingDB (2024) · UC San Diego · doi:10.7270/q2x352pq
BindingDB Entry 50018114: Homobivalent, Trivalent, and Covalent PROTACs: Emerging Strategies for Protein Degradation.
BindingDB (2024) · UC San Diego · doi:10.7270/q2833x64
BindingDB Entry 50018947: Structural rationalization of GSPT1 and IKZF1 degradation by thalidomide molecular glue derivatives.
BindingDB (2024) · UC San Diego · doi:10.7270/q2v12923
BindingDB Entry 50021508: Serendipitous discovery of Class I HDAC inhibitors from rational design of molecular glue degraders targeting HDAC.
BindingDB (2025) · UC San Diego · doi:10.7270/q22230df
BindingDB Entry 50012397: Discovery of a Napabucasin PROTAC as an Effective Degrader of the E3 Ligase ZFP91.
BindingDB (2022) · UC San Diego · doi:10.7270/q2qn6bfx
BindingDB Entry 50011836: Design and synthesis of selective degraders of EGFR
BindingDB (2022) · UC San Diego · doi:10.7270/q2pg1wcq
BindingDB Entry 50022109: An overview of PROTACs targeting MDM2 as a novel approach for cancer therapy.
BindingDB (2025) · UC San Diego · doi:10.7270/q2wq08f2
BindingDB Entry 50020409: Current advances of small molecule E3 ligands for proteolysis-targeting chimeras design.
BindingDB (2024) · UC San Diego · doi:10.7270/q2pv6qt5

Authors: Yang, J., Li, Y., Aguilar, A., Liu, Z., Yang, C.-Y., & Wang, S.
Affiliations: University of Michigan (US)
Corresponding author: Wang, Shaomeng
ORCID: Yang, Jiuling
Aguilar, Angelo
Liu, Zhaomin
Yang, Chao-Yie
Wang, Shaomeng
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2019-09-27
Volume: 62
Issue: 21
Pages: 9471-9487
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/acs.jmedchem.9b00846
PMC: PMC7354697
OpenAlex: W2976352578
Cited by: 190
References: 45
Citations by year: 2026: 17 · 2025: 39 · 2024: 31 · 2023: 23 · 2022: 30 · 2021: 25 · 2020: 24 · 2019: 1
FWCI: 6.95
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-045 (stm-asf)
Locations: Journal of Medicinal Chemistry (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Health and Human Services (1R01CA208267, P30 CA046592)
University of Michigan
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 › Ubiquitin and proteasome pathways
Keywords: PROTAC degraders, molecular glues, MDM2, GSPT1, structural modification, protein degradation, translation termination factor, anticancer drug design
MeSH terms: Antineoplastic Agents, Humans, Models, Molecular, Peptide Termination Factors, Protein Conformation, Drug Design, Cell Line, Tumor, Proto-Oncogene Proteins c-mdm2, Proteolysis

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Simple Structural Modifications Converting a Bona fide MDM2 PROTAC Degrader into a Molecular Glue Molecule: A Cautionary Tale in the Design of PROTAC Degraders

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