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Phthalimide conjugation as a strategy for in vivo target protein degradation
Open accessAbstract
The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem. In part, this is because many small-molecule antagonists disrupt the activity of only one domain in the target protein. We devised a chemical strategy that promotes ligand-dependent target protein degradation using as an example the transcriptional coactivator BRD4, a protein critical for cancer cell growth and survival. We appended a competitive antagonist of BET bromodomains to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The resultant compound, dBET1, induced highly selective cereblon-dependent BET protein degradation in vitro and in vivo and delayed leukemia progression in mice. A second series of probes resulted in selective degradation of the cytosolic protein FKBP12. This chemical strategy for controlling target protein stability may have implications for therapeutically targeting previously intractable proteins.
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“By conjugating JQ1 to a thalidomide derivative, dBet1 successfully recruited cRBN to induce rapid and selective degradation of BRD2, BRD3 and BRD4.”
From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as Winter et al. 2015
In the citing paper
“The majority of degraders recruit the CUL4-RBX1-DDB1-CRBN (CRL4crbn) (Ito et al., 2010; Kronke et al., 2014; Winter et al., 2015), or CUL2-RBX1-ElonginB-ElonginC-VHL (CRL2vhl) (Buckley et al., 2012; Galdeano et al., 2014) E3 ligases to ubiquitinate a POI.”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Winter et al., 2015
In the citing paper
“Degraders result in loss of both enzymatic and non-enzymatic functions of proteins, such as the scaffolding function of kinases (Cromm et al., 2018), or the gene regulatory functions of transcriptional effectors (Winter et al., 2015).”
From Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development (2020) · cites this paper as Winter et al., 2015
In the citing paper
“the inhibition of BET proteins with SMIs is relatively well tolerated than their degradation with PROTAC dBET1 [25].”
From PROteolysis TArgeting Chimeras (PROTACs) as emerging anticancer therapeutics (2020) · cites this paper as [25]
In the citing paper
“PROTACs consisting of pomalidomide and OTX015 [84] or JQ1 [85] resulted in robust BRD4 degradation when used at low nanomolar concentrations [84, 85].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [85]
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Cites
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262
Self-citationSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
Lovén, J., Hoke, H. A., Lin, C. Y., Lau, A., Orlando, D. A., Vakoc, C. R., Bradner, J. E., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.036 · Cited by 2,961
Self-citationBET Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc
Delmore, J. E., Issa, G. C., Lemieux, M. E., Rahl, P. B., Shi, J., Jacobs, H. M., Kastritis, E., Gilpatrick, T., Paranal, R. M., Qi, J., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.017 · Cited by 2,888
Self-citationSakamoto, 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
Integration, scaling, space-group assignment and post-refinement
Kabsch, W. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909047374 · Cited by 2,554
Function and regulation of cullin–RING ubiquitin ligases
Petroski, M. D., & Deshaies, R. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1547 · Cited by 2,148
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
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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
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Bradner, J. E., Hnisz, D., & Young, R. A. (2017) · Cell · doi:10.1016/j.cell.2016.12.013 · Cited by 1,221
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Nabet, B., Roberts, J. M., Buckley, D. L., Paulk, J., Dastjerdi, S., Yang, A., Leggett, A. L., Erb, M. A., Lawlor, M. A., Souza, A., et al. (2018) · Nature Chemical Biology · doi:10.1038/s41589-018-0021-8 · Cited by 1,118
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Zou, S., Tong, Q., Liu, B., Huang, W., Tian, Y., & Fu, X. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01258-7 · Cited by 1,109
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Zhou, B. N., Hu, J., Xu, F., Chen, Z., Bai, L., Fernández‐Salas, E., Lin, M., Liu, L., Yang, C., Zhao, Y., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01816 · Cited by 376
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Ward, C. C., Kleinman, J. I., Brittain, S. M., Lee, P. S., Chung, C. Y. S., Kim, K., Petri, Y., Thomas, J. R., Tallarico, J. A., McKenna, J. M., et al. (2019) · ACS Chemical Biology · doi:10.1021/acschembio.8b01083 · Cited by 336
Zoppi, V., Hughes, S. J., Maniaci, C., Testa, A., Gmaschitz, T., Wieshofer, C., Koegl, M., Riching, K. M., Daniels, D. L., Spallarossa, A., et al. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01413 · Cited by 336
Degradation of proteins by PROTACs and other strategies
Wang, Y., Jiang, X., Feng, F., Liu, W., & Sun, H. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2019.08.001 · Cited by 335
WD40 repeat domain proteins: a novel target class?
Schapira, M., Tyers, M., Torrent, M., & Arrowsmith, C. H. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.179 · Cited by 335
PHOTACs enable optical control of protein degradation
Reynders, M., Matsuura, B. S., Bérouti, M., Simoneschi, D., Marzio, A., Pagano, M., & Trauner, D. H. (2020) · Science Advances · doi:10.1126/sciadv.aay5064 · Cited by 337
Dai, X., Gan, W., Li, X., Wang, S., Zhang, W., Huang, L., Liu, S., Zhong, Q., Guo, J., Zhang, J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4378 · Cited by 349
Self-citationTranscription control by the ENL YEATS domain in acute leukaemia
Erb, M. A., Scott, T. G., Li, B. E., Xie, H., Paulk, J., Seo, H., Souza, A., Roberts, J. M., Dastjerdi, S., Buckley, D. L., et al. (2017) · Nature · doi:10.1038/nature21688 · Cited by 313
Self-citationTargeted protein degradation: advances in drug discovery and clinical practice
Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326
Drug Discovery Targeting Bromodomain-Containing Protein 4
Liu, Z., Wang, P., Chen, H., Wold, E. A., Tian, B., Brasier, A. R., & Zhou, J. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01761 · Cited by 328
Target and tissue selectivity of PROTAC degraders
Guenette, R. G., Yang, S. W., Min, J., Pei, B., & Potts, P. R. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00200k · Cited by 324
Takeda, D. Y., Spisák, S., Seo, J.-H., Bell, C., O’Connor, E., Korthauer, K., Ribli, D., Csabai, I., Solymosi, N., Szállási, Z., et al. (2018) · Cell · doi:10.1016/j.cell.2018.05.037 · Cited by 317
Quantitative Live-Cell Kinetic Degradation and Mechanistic Profiling of PROTAC Mode of Action
Riching, K. M., Mahan, S. D., Corona, C. R., McDougall, M. G., Vasta, J. D., Robers, M. B., Urh, M., & Daniels, D. L. (2018) · ACS Chemical Biology · doi:10.1021/acschembio.8b00692 · Cited by 310
Reversible Spatiotemporal Control of Induced Protein Degradation by Bistable PhotoPROTACs
Pfaff, P., Samarasinghe, K. T. G., Crews, C. M., & Carreira, E. M. (2019) · ACS Central Science · doi:10.1021/acscentsci.9b00713 · Cited by 320
Chemistries of bifunctional PROTAC degraders
Cao, C., He, M., Wang, L., He, Y., & Rao, Y. (2022) · Chemical Society Reviews · doi:10.1039/d2cs00220e · Cited by 313
Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312
Lu, M., Liu, T., Jiao, Q., Ji, J., Tao, M., Liu, Y., You, Q., & Jiang, Z. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.01.063 · Cited by 310
The PROTAC technology in drug development
Zou, Y., Ma, D., & Wang, Y. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3369 · Cited by 312
Light-induced control of protein destruction by opto-PROTAC
Liu, J., Chen, H., Ma, L., He, Z., Wang, D., Liu, Y., Lin, Q., Zhang, T., Gray, N. S., Kanıskan, H. Ü., et al. (2020) · Science Advances · doi:10.1126/sciadv.aay5154 · Cited by 310
PROTAC: An Effective Targeted Protein Degradation Strategy for Cancer Therapy
Qi, S., Dong, J., Xu, Z., Cheng, X., Zhang, W., & Qin, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.692574 · Cited by 306
Small-Molecule Modulation of Protein Homeostasis
Burslem, G. M., & Crews, C. M. (2017) · Chemical Reviews · doi:10.1021/acs.chemrev.7b00077 · Cited by 298
Sun, Y., Zhao, X., Ding, N., Gao, H., Wu, Y., Yang, Y., Zhao, M., Hwang, J., Song, Y., Liu, W., et al. (2018) · Cell Research · doi:10.1038/s41422-018-0055-1 · Cited by 295
Epigenetics and approaches to targeted epigenetic therapy in acute myeloid leukemia
Wouters, B. J., & Delwel, R. (2015) · Blood · doi:10.1182/blood-2015-07-604512 · Cited by 300
Metadata
- Authors
- Winter, G. E., Buckley, D. L., Paulk, J., Roberts, J. M., Souza, A., Dhe-Paganon, S., & Bradner, J. E.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
- Harvard University (US)
- Corresponding author
- Winter, Georg E.
- Buckley, Dennis L.
- Bradner, James E.
- Venue
- Science
- Published
- 2015-06-19
- Volume
- 348
- Issue
- 6241
- Pages
- 1376-1381
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4937790
- OpenAlex
- W1565539350
- Cited by
- 1,760
- References
- 38
- Citations by year
- 2026: 145 · 2025: 191 · 2024: 200 · 2023: 157 · 2022: 189 · 2021: 203 · 2020: 206 · 2019: 161 · 2018: 110 · 2017: 116 · 2016: 59 · 2015: 19
- FWCI
- 44.41
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01-CA176745, P01-CA066996)
- Damon Runyon Cancer Research Foundation (DRG-2196-14)
- Marc Cohen and Alain Cohen
- William Lawrence and Blanche Hughes Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- BRD4, FKBP12, transcriptional coactivator, transcription factor inhibitors, leukemia, protein stability, small molecule antagonists
- MeSH terms
- Bromodomain Containing Proteins, Animals, Azepines, Disease Models, Animal, Ligands, Nuclear Proteins, Peptide Hydrolases, Phthalimides, Thalidomide, Transcription Factors, Drug Design, Leukemia, Promyelocytic, Acute, Protein Structure, Tertiary, Crystallography, X-Ray, Cell Cycle Proteins, Tacrolimus Binding Protein 1A, Ubiquitin-Protein Ligases, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice, Protein Stability, Molecular Targeted Therapy, Proteolysis
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