Cited by 69Protein Degradation and InhibitorsChemical Synthesis and AnalysisUbiquitin and proteasome pathways

Monomeric Targeted Protein Degraders

Hanan, Emily J., Liang, Jun, Wang, Xiaojing, Blake, Robert A., Blaquiere, Nicole, Staben, Steven T.·2020·Journal of Medicinal Chemistry

Abstract

The discovery and development of targeted protein degraders have become important areas of research in the field of medicinal chemistry. Inducing degradation of a target protein presents several advantages relative to simple inhibition including a potential for extended duration of action and more profound pharmacology. While engineered heterodimeric molecules have recently been a major focus within industry and academia, this Perspective highlights examples of targeted protein degradation observed for smaller, monomeric molecules. Methods and tools for evaluating protein degradation as well as a discussion of physical properties of monomeric vs engineered heterodimeric degraders are presented.

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Crossref · 10.1021/acs.jmedchem.0c00093

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218 of 218 references verified0 citation errors · 0 not checkable

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  • MG degraders have favorable drug-like properties that often fall within Lipinski's rule of 5.

    “(i) favorable drug-like properties that often fall within the Lipinski's ''rule of 5'' (Fig. 2); 35”

    From Chasing molecular glue degraders: screening approaches (2022) · cites this paper as [35]

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Authors
Hanan, E. J., Liang, J., Wang, X., Blake, R. A., Blaquiere, N., & Staben, S. T.
Affiliations
  • Genentech (US)
  • Genentech, Inc. , , 1 DNA Way , , ,
Corresponding author
Staben, Steven T.
Venue
Journal of Medicinal Chemistry
Published
2020-04-30
Volume
63
Issue
20
Pages
11330-11361
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W3023538604
Cited by
69
References
218
Citations by year
2026: 6 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 13 · 2021: 13 · 2020: 8
FWCI
1.20
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
targeted protein degradation, duration of action
MeSH terms
Binding Sites, Humans, Protein Binding, Proteins, Molecular Structure, Ubiquitin-Protein Ligases, Cell Line, Tumor, Small Molecule Libraries, Drug Discovery, Proteolysis

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