The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation
Abstract
Proteolysis targeting chimeras (PROTACs) are bispecific molecules containing a target protein binder and an ubiquitin ligase binder connected by a linker. By recruiting an ubiquitin ligase to a target protein, PROTACs promote ubiquitination and proteasomal degradation of the target protein. The generation of effective PROTACs depends on the nature of the protein/ligase ligand pair, linkage site, linker length, and linker composition, all of which have been difficult to address in a systematic way. Herein, we describe a "click chemistry" approach for the synthesis of PROTACs. We demonstrate the utility of this approach with the bromodomain and extraterminal domain-4 (BRD4) ligand JQ-1 (3) and ligase binders targeting cereblon (CRBN) and Von Hippel-Lindau (VHL) proteins. An AlphaScreen proximity assay was used to determine the ability of PROTACs to form the ternary ligase-PROTAC-target protein complex and a MSD assay to measure cellular degradation of the target protein promoted by PROTACs.
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Cites
Selective inhibition of BET bromodomains
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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
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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A Comprehensive Mathematical Model for Three-Body Binding Equilibria
Douglass, E. F., Miller, C. J., Sparer, G., Shapiro, H., & Spiegel, D. A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja311795d · Cited by 472
Protein Degradation by In-Cell Self-Assembly of Proteolysis Targeting Chimeras
Lebraud, H., Wright, D. J., Johnson, C. N., & Heightman, T. D. (2016) · ACS Central Science · doi:10.1021/acscentsci.6b00280 · Cited by 413
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Cited by
Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of ageing
Boland, B., Yu, W. H., Corti, O., Mollereau, B., Henriques, A., Bezard, E., Pastores, G. M., Rubinsztein, D. C., Nixon, R. A., Duchen, M. R., et al. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2018.109 · Cited by 558
Proteolysis-targeting chimera (PROTAC) for targeted protein degradation and cancer therapy
Li, X., & Song, Y. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00885-3 · Cited by 521
Edmondson, S. D., Yang, B., & Fallan, C. (2019) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2019.04.030 · Cited by 422
Current strategies for the design of PROTAC linkers: a critical review
Troup, R. I., Fallan, C., & Baud, M. G. J. (2020) · Exploration of Targeted Anti-tumor Therapy · doi:10.37349/etat.2020.00018 · Cited by 424
“[87], probed the effects of linker length and ligase ligand on a series of BRD4 targeting PROTACs (Figure 11).”
BackgroundDegradation 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
Metadata
- Authors
- Wurz, R. P., Dellamaggiore, K., Dou, H., Javier, N., Lo, M.-C., McCarter, J. D., Mohl, D., Sastri, C., Lipford, J. R., & Cee, V. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2017-04-17
- Volume
- 61
- Issue
- 2
- Pages
- 453-461
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2604744033
- Cited by
- 205
- References
- 8
- FWCI
- 5.92
- Type
- journal article
- Language
- en
- Open access
- closed
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- Wurz, R. P., Dellamaggiore, K., Dou, H., Javier, N., Lo, M.-C., McCarter, J. D., Mohl, D., Sastri, C., Lipford, J. R., & Cee, V. J. (2018). A “Click Chemistry Platform” for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.6b01781
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