Intrinsically disordered proteins and biomolecular condensates as drug targets
Open accessAbstract
Intrinsically disordered domains represent attractive therapeutic targets because they play key roles in cancer, as well as in neurodegenerative and infectious diseases. They are, however, considered undruggable because they do not form stable binding pockets for small molecules and, therefore, have not been prioritized in drug discovery. Under physiological solution conditions many biomedically relevant intrinsically disordered proteins undergo phase separation processes leading to the formation of mesoscopic highly dynamic assemblies, generally known as biomolecular condensates that define environments that can be quite different from the solutions surrounding them. In what follows, we review key recent findings in this area and show how biomolecular condensation can offer opportunities for modulating the activities of intrinsically disordered targets.
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Transcription factors, intrinsically disordered proteins, and scaffolding proteins are among the compelling targets outside the reach of small-molecule discovery approaches.
“This includes, among others, transcription factors or other intrinsically disordered proteins, as well as scaffolding proteins.4,5”
From Advancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence (2023) · cites this paper as [5]
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Lindorff-Larsen, K., & Kragelund, B. B. (2021) · Journal of Molecular Biology · doi:10.1016/j.jmb.2021.167196 · Cited by 85 · see citing works
Rational optimization of a transcription factor activation domain inhibitor
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Self-citationAdvancing Targeted Protein Degradation via Multiomics Profiling and Artificial Intelligence
Duran-Frigola, M., Cigler, M., & Winter, G. E. (2023) · Journal of the American Chemical Society · doi:10.1021/jacs.2c11098 · Cited by 50 · see citing works
Varadi, M., Bordin, N., Orengo, C., & Velankar, S. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102543 · Cited by 29 · see citing works
- Authors
- Biesaga, M., Frigolé-Vivas, M., & Salvatella, X.
- Affiliations
- Institute for Research in Biomedicine (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Corresponding author
- Salvatella, Xavier
- Venue
- Current Opinion in Chemical Biology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 62
- Pages
- 90-100
- ISSN
- 1367-5931 (ISSN-L)
- PMC
- PMC7616887
- OpenAlex
- W3149136862
- Cited by
- 115
- References
- 97
- Citations by year
- 2026: 14 · 2025: 32 · 2024: 20 · 2023: 24 · 2022: 20 · 2021: 5
- FWCI
- 1.81
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Current Opinion in Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
- Funders
- European Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- intrinsically disordered proteins, biomolecular condensates, phase separation, undruggable targets, drug discovery, cancer, neurodegenerative diseases, infectious diseases, liquid-liquid phase separation, protein condensates
- MeSH terms
- Pharmaceutical Preparations, Humans, Protein Binding, Pyrimidines, Structure-Activity Relationship, Thermodynamics, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, Transition Temperature, Phase Transition, Protein Multimerization, Drug Discovery, Intrinsically Disordered Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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