Activity-based protein profiling for mapping and pharmacologically interrogating proteome-wide ligandable hotspots
Open accessAbstract
Despite the completion of human genome sequencing efforts nearly 15 years ago that brought with it the promise of genome-based discoveries that would cure human diseases, most protein targets that control human diseases have remained largely untranslated, in-part because they represent difficult protein targets to drug. In addition, many of these protein targets lack screening assays or accessible binding pockets, making the development of small-molecule modulators very challenging. Here, we discuss modern methods for activity-based protein profiling-based chemoproteomic strategies to map 'ligandable' hotspots in proteomes using activity and reactivity-based chemical probes to allow for pharmacological interrogation of these previously difficult targets. We will showcase several recent examples of how these technologies have been used to develop highly selective small-molecule inhibitors against disease-related protein targets.
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Chemoproteomic platforms enable rapid target identification and selectivity profiling of covalent ligands.
“This ‘electrophile-first’ approach is partly facilitated by the development of chemoproteomic platforms that enable rapid target identification and selectivity profiling of covalent ligands14–18.”
From Advances in covalent drug discovery (2022) · cites this paper as [15]
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- [6]Counihan JL Ford B Nomura DK Mapping proteome-wide interactions of reactive chemicals using chemoproteomic platforms Curr. Opin. Chem. Biol 2016 30 68 76 26647369 PMC4731263
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- Authors
- Roberts, A. M., Ward, C. C., & Nomura, D. K.
- Affiliations
- University of California, Berkeley (US)
- Corresponding author
- Nomura, Daniel K
- Venue
- Current Opinion in Biotechnology
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 43
- Pages
- 25-33
- ISSN
- 0958-1669 (ISSN-L)
- PMC
- PMC5305418
- OpenAlex
- W2508431262
- Cited by
- 108
- References
- 49
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 11 · 2023: 17 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 13 · 2018: 6 · 2017: 10
- FWCI
- 0.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 206 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Opinion in Biotechnology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (R01CA172667)
- American Cancer Society (RSG14-242-01-TBE)
- U.S. Department of Defense (CDMRP W81XWH-15-1-0050)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Click Chemistry and Applications
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Keywords
- activity-based protein profiling, chemoproteomics, small molecule inhibitors, drug target identification
- MeSH terms
- Animals, Humans, Proteins, Drug Design, Biomarkers, Proteome, Protein Array Analysis
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