ArticleJournal of biomolecular screening2014
Time-Resolved Fluorescence Resonance Energy Transfer Assay for Discovery of Small-Molecule Inhibitors of Methyl-CpG Binding Domain Protein 2.
Article in Journal of biomolecular screening, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Article
- Chromatin accessibility: biological functions, molecular mechanisms and therapeutic application.Signal transduction and targeted therapy · 2024Review
- Design, synthesis, and evaluation of a mitoxantrone probe (MXP) for biological studies.Bioorganic & medicinal chemistry letters · 2023Article
- A screen for MeCP2-TBL1 interaction inhibitors using a luminescence-based assay.Scientific reports · 2023Article
- Computational discovery of novel inhibitory candidates targeting versatile transcriptional repressor MBD2.Journal of molecular modeling · 2022Article
- Inhibitors of DNA Methylation.Advances in experimental medicine and biology · 2022Review
- Review
- Article
- Prostate Cancer Epigenetics: From Basic Mechanisms to Clinical Implications.Cold Spring Harbor perspectives in medicine · 2019Review
- BAI1 Suppresses Medulloblastoma Formation by Protecting p53 from Mdm2-Mediated Degradation.Cancer cell · 2018Article
- Readers of DNA methylation, the MBD family as potential therapeutic targets.Pharmacology & therapeutics · 2018Review
- Advances in discovering small molecules to probe protein function in a systems context.Current opinion in chemical biology · 2016Review
- Natural compound-derived epigenetic regulators targeting epigenetic readers, writers and erasers.Current topics in medicinal chemistry · 2016Review
- Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.Biochimica et biophysica acta · 2014Review
- Prostate cancer epigenetics and its clinical implications.Asian journal of andrologyReview
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Methylated DNA binding proteins such as Methyl-CpG Binding Domain Protein 2 (MBD2) can transduce DNA methylation alterations into a repressive signal by recruiting transcriptional co-repressor complexes. Interfering with MBD2 could lead to reactivation of tumor suppressor genes and therefore represents an attractive strategy for epigenetic therapy. We developed and compared fluorescence polarization (FP) and time-resolved fluorescence resonance energy transfer (TR-FRET)-based high-throughput screening (HTS) assays to identify small-molecule inhibitors of the interaction between the methyl binding domain of MBD2 (MBD2-MBD) and methylated DNA. Although both assays performed well in 96-well format, the TR-FRET assay (Z' factor = 0.58) emerged as a superior screening strategy compared with FP (Z' factor = 0.08) when evaluated in an HTS 384-well plate format. Using TR-FRET, we screened the Sigma LOPAC library for MBD2-MBD inhibitors and identified four compounds that also validated in a dose-response series. This included two known DNA intercalators (mitoxantrone and idarubicin) among two other inhibitory compounds (NF449 and aurintricarboxylic acid). All four compounds also inhibited the binding of SP-1, a transcription factor with a GC-rich binding sequence, to a methylated oligonucleotide, demonstrating that the activity was nonspecific. Our results provide proof of principle for using TR-FRET-based HTS to identify small-molecule inhibitors of MBD2 and other DNA-protein interactions.
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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.