The DOI matches its Crossref record; 112 of the 112 references it cites were found in a registry or an index.
Targeted Protein Degradation by Small Molecules
Open accessAbstract
Protein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins. Here, we review recent advances in the use of small molecules to degrade proteins in a selective manner. First, we highlight all-small-molecule techniques with direct clinical application. Second, we describe techniques that may find broader acceptance in the biomedical research community that require little or no synthetic chemistry. In addition to serving as innovative research tools, these new approaches to control intracellular protein levels offer the potential to develop novel therapeutics targeting proteins that are not currently pharmaceutically vulnerable.
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“Moreover, the catalytic nature of PROTAC can achieve and maintain enhanced target degradation at low doses (23, 25).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [25]
Experimental — accuracy not yet measuredIn the citing paper
“PROTACs can achieve high cellular potency due to their catalytic rather than occupancy-based mechanism of action 11,14,22”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [22]
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Identification of a Primary Target of Thalidomide Teratogenicity
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Research works printed but not linked: 1
- Huggins C, 1941, Cancer Res, 168, 293
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Metadata
- Authors
- Bondeson, D. P., & Crews, C. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Crews, Craig M.
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2017-01-06
- Volume
- 57
- Issue
- 1
- Pages
- 107-123
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- PMC
- PMC5586045
- OpenAlex
- W2530302741
- Cited by
- 207
- References
- 112
- Citations by year
- 2026: 25 · 2025: 34 · 2024: 15 · 2023: 17 · 2022: 17 · 2021: 24 · 2020: 22 · 2019: 32 · 2018: 13 · 2017: 7
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (F99CA212229, R35CA197589)
- National Institute of General Medical Sciences (T32GM007223)
- 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
- targeted protein degradation, small molecules, proteostasis, selective protein degradation, drug repurposing, therapeutic target, research tools
- MeSH terms
- Animals, Humans, Oligopeptides, Proteins, Drug Delivery Systems, Small Molecule Libraries, Proteolysis
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