ArticleScientific reports2015
Discovery of Small Molecules that Inhibit the Disordered Protein, p27(Kip1).
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Liquid-liquid phase separation drives immune signaling transduction in cancer: a bibliometric and visualized study from 1992 to 2024.Frontiers in oncology · 2025Pooled it
- Toward a unified framework for determining conformational ensembles of disordered proteins.Nature methods · 2026Review
- How small molecules stabilize oligomers of a phase-separating disordered protein.bioRxiv : the preprint server for biology · 2025Article
- Article
- Targeting protein disorder: the next hurdle in drug discovery.Nature reviews. Drug discovery · 2025Review
- DIRseq: a method for predicting drug-interacting residues of intrinsically disordered proteins from sequences.bioRxiv : the preprint server for biology · 2025Article
- Ensemble Docking for Intrinsically Disordered Proteins.Journal of chemical information and modeling · 2025Article
- Covalent Adducts Formed by the Androgen Receptor Transactivation Domain and Small Molecule Drugs Remain Disordered.Journal of chemical information and modeling · 2025Article
- Ensemble docking for intrinsically disordered proteins.bioRxiv : the preprint server for biology · 2025Article
- IDRdecoder: a machine learning approach for rational drug discovery toward intrinsically disordered regions.Frontiers in bioinformatics · 2025Article
- HES1 is required for mouse fetal hematopoiesis.Stem cell research & therapy · 2024Article
- Picosecond Dynamics of a Small Molecule in Its Bound State with an Intrinsically Disordered Protein.Journal of the American Chemical Society · 2024Article
- Challenges and opportunities in cell expansion for cultivated meat.Frontiers in nutrition · 2024Article
- Defining the condensate landscape of fusion oncoproteins.Nature communications · 2023Article
- Therapeutic targeting of CNBP phase separation inhibits ribosome biogenesis and neuroblastoma progression via modulating SWI/SNF complex activity.Clinical and translational medicine · 2023Article
- Review
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
- Chemical tools for study and modulation of biomolecular phase transitions.Chemical science · 2022Review
- Modulating biomolecular condensates: a novel approach to drug discovery.Nature reviews. Drug discovery · 2022Review
- Small molecule SJ572946 activates BAK to initiate apoptosis.iScience · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Disordered proteins are highly prevalent in biological systems, they control myriad signaling and regulatory processes, and their levels and/or cellular localization are often altered in human disease. In contrast to folded proteins, disordered proteins, due to conformational heterogeneity and dynamics, are not considered viable drug targets. We challenged this paradigm by identifying through NMR-based screening small molecules that bound specifically, albeit weakly, to the disordered cell cycle regulator, p27(Kip1) (p27). Two groups of molecules bound to sites created by transient clusters of aromatic residues within p27. Conserved chemical features within these two groups of small molecules exhibited complementarity to their binding sites within p27, establishing structure-activity relationships for small molecule:disordered protein interactions. Finally, one compound counteracted the Cdk2/cyclin A inhibitory function of p27 in vitro, providing proof-of-principle that small molecules can inhibit the function of a disordered protein (p27) through sequestration in a conformation incapable of folding and binding to a natural regulatory target (Cdk2/cyclin A).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.