ArticleScience advances2019
Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2.
Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Epigenomic Modulators and Thyroid Hormone Receptor β Agonists: A New Paradigm for Tumor Suppression in Thyroid Cancer.Endocrinology · 2025Review
- Targeting redox-sensitive MBD2-NuRD condensate in cancer cells.Nature cell biology · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Long way up: rethink diseases in light of phase separation and phase transition.Protein & cell · 2024Review
- Methyl-CpG binding domain protein 2 (Mbd2) drives breast cancer progression through the modulation of epithelial-to-mesenchymal transition.Experimental & molecular medicine · 2024Article
- Multi-level functional genomics reveals molecular and cellular oncogenicity of patient-based 3' untranslated region mutations.Cell reports · 2023Article
- Article
- Intrinsically Disordered Proteins: An Overview.International journal of molecular sciences · 2022Review
- Computational discovery of novel inhibitory candidates targeting versatile transcriptional repressor MBD2.Journal of molecular modeling · 2022Article
- A FRET-Based Biosensor for the Src N-Terminal Regulatory Element.Biosensors · 2022Article
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Unique protein interaction networks define the chromatin remodelling module of the NuRD complex.The FEBS journal · 2022Article
- Intrinsically disordered proteins and biomolecular condensates as drug targets.Current opinion in chemical biology · 2021Review
- Computational strategy for intrinsically disordered protein ligand design leads to the discovery of p53 transactivation domain I binding compounds that activate the p53 pathway.Chemical science · 2020Article
- Roles, Characteristics, and Analysis of Intrinsically Disordered Proteins: A Minireview.Life (Basel, Switzerland) · 2020Review
- Liquid-Liquid Phase Separation by Intrinsically Disordered Protein Regions of Viruses: Roles in Viral Life Cycle and Control of Virus-Host Interactions.International journal of molecular sciences · 2020Review
- Drug Discovery Targeting the Disorder-To-Order Transition Regions through the Conformational Diversity Mimicking and Statistical Analysis.International journal of molecular sciences · 2020Article
- Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although intrinsically disordered protein regions (IDPRs) are commonly engaged in promiscuous protein-protein interactions (PPIs), using them as drug targets is challenging due to their extreme structural flexibility. We report a rational discovery of inhibitors targeting an IDPR of MBD2 that undergoes disorder-to-order transition upon PPI and is critical for the regulation of the Mi-2/NuRD chromatin remodeling complex (CRC). Computational biology was essential for identifying target site, searching for promising leads, and assessing their binding feasibility and off-target probability. Molecular action of selected leads inhibiting the targeted PPI of MBD2 was validated in vitro and in cell, followed by confirming their inhibitory effects on the epithelial-mesenchymal transition of various cancer cells. Identified lead compounds appeared to potently inhibit cancer metastasis in a murine xenograft tumor model. These results constitute a pioneering example of rationally discovered IDPR-targeting agents and suggest Mi-2/NuRD CRC and/or MBD2 as a promising target for treating cancer metastasis.
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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.