Cited by 207Protein Degradation and InhibitorsUbiquitin and proteasome pathwaysChemical Synthesis and Analysis

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Targeted Protein Degradation by Small Molecules

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Bondeson, Daniel P., Crews, Craig M.·2017·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev-pharmtox-010715-103507PMC PMC5586045

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Abstract

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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Authors: Bondeson, D. P., & Crews, C. M.
Affiliations: Yale University (US)
Corresponding author: Crews, Craig M.
ORCID: Bondeson, Daniel P.
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
DOI: 10.1146/annurev-pharmtox-010715-103507
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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