Targeting the Undruggable Proteome: The Small Molecules of My Dreams
Open accessAbstract
Biologically active small molecules have long proven useful in the exploration of cell biology. Although many early compounds were by-products of drug development efforts, recent increased small molecule screening efforts in academia have expanded the repertoire of biological processes investigated to include areas of biology that are not of immediate pharmaceutical interest. Many of these new bioassays score for small molecule-induced phenotypic changes at the cellular or even organismal level and thus have been described as "chemical genetic" screens. However, this analogy with traditional genetic screens is misleading; although each gene has roughly an equivalent chance of being mutated in a traditional genetic screen, the amount of "proteomic space" that a chemical genetics approach can reach using current small molecule libraries is considerably smaller. Thus, new chemical biology methodologies are needed to target the remaining "undruggable proteome" with small druglike molecules.
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With the potential to degrade nearly 80% of human intracellular proteins, PROTAC technology has broad applications across various fields, most notably in cancer therapy.
“With the potential to degrade nearly 80% of human intracellular proteins, PROTAC technology has broad applications across various fields, most notably in cancer therapy.483”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [483]
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- Authors
- Crews, C. M.
- Affiliations
- Yale University (US)
- Corresponding author
- Crews, Craig M.
- ORCID
- Crews, Craig M.
- Venue
- Chemistry & Biology
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 17
- Issue
- 6
- Pages
- 551-555
- ISSN
- 1074-5521 (ISSN-L)
- PMC
- PMC2925121
- OpenAlex
- W2074440680
- Cited by
- 147
- References
- 46
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 15 · 2023: 17 · 2022: 10 · 2021: 21 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 5 · 2013: 7 · 2012: 8
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Chemistry & Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (R33CA118631)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Keywords
- small molecules, chemical genetics, chemical screen, small molecule library, phenotypic assays, drug discovery, chemical biology
- MeSH terms
- Animals, Genetics, Humans, Drug Design, Proteome, Small Molecule Libraries, High-Throughput Screening Assays
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