ArticleNucleic acids research2008
Direct inhibition of the DNA-binding activity of POU transcription factors Pit-1 and Brn-3 by selective binding of a phenyl-furan-benzimidazole dication.
Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 51 citations in OpenAlex.
- Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.Nature genetics · 2024Article
- Single GC base pair recognition by a heterocyclic diamidine: structures, affinities, and dynamics.RSC advances · 2024Article
- Induction of AML cell differentiation using HOXA9/DNA binding inhibitors as a potential therapeutic option for HOXA9-dependent AML.HemaSphere · 2024Article
- Binding to the DNA Minor Groove by Heterocyclic Dications: from AT Specific to GC Recognition Compounds.Current protocols · 2023Review
- Heterocyclic Diamidine DNA Ligands as HOXA9 Transcription Factor Inhibitors: Design, Molecular Evaluation, and Cellular Consequences in a HOXA9-Dependant Leukemia Cell Model.Journal of medicinal chemistry · 2019Article
- Targeting Transcription Factors for Cancer Treatment.Molecules (Basel, Switzerland) · 2018Review
- Breast cancer metastasis to liver and lung is facilitated by Pit-1-CXCL12-CXCR4 axis.Oncogene · 2018Article
- An Aromatic Diamidine That Targets Kinetoplast DNA, Impairs the Cell Cycle in Trypanosoma cruzi, and Diminishes Trypomastigote Release from Infected Mammalian Host Cells.Antimicrobial agents and chemotherapy · 2016Article
- Resolution of mixed site DNA complexes with dimer-forming minor-groove binders by using electrospray ionization mass spectrometry: compound structure and DNA sequence effects.Chemistry (Weinheim an der Bergstrasse, Germany) · 2015Article
- Structure-dependent binding of arylimidamides to the DNA minor groove.Chembiochem : a European journal of chemical biology · 2014Article
- Structure-dependent inhibition of the ETS-family transcription factor PU.1 by novel heterocyclic diamidines.Nucleic acids research · 2014Article
- The neural crest transcription factor Brn3a is expressed in melanoma and required for cell cycle progression and survival.EMBO molecular medicine · 2013Article
- Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines.Nucleic acids research · 2013Article
- Binding to the DNA minor groove by heterocyclic dications: from AT-specific monomers to GC recognition with dimers.Current protocols in nucleic acid chemistry · 2012Review
- Discovery of a novel, monocationic, small-molecule inhibitor of scrapie prion accumulation in cultured sheep microglia and Rov cells.PloS one · 2012Article
- Water-mediated binding of agents that target the DNA minor groove.Journal of the American Chemical Society · 2011Article
- Induced topological changes in DNA complexes: influence of DNA sequences and small molecule structures.Nucleic acids research · 2011Article
- Deregulation of the Pit-1 transcription factor in human breast cancer cells promotes tumor growth and metastasis.The Journal of clinical investigation · 2010Article
- DNA minor groove induced dimerization of heterocyclic cations: compound structure, binding affinity, and specificity for a TTAA site.Journal of molecular biology · 2010Article
- Dual FRET assay for detecting receptor protein interaction with DNA.Nucleic acids research · 2010Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The development of small molecules to control gene expression could be the spearhead of future-targeted therapeutic approaches in multiple pathologies. Among heterocyclic dications developed with this aim, a phenyl-furan-benzimidazole dication DB293 binds AT-rich sites as a monomer and 5'-ATGA sequence as a stacked dimer, both in the minor groove. Here, we used a protein/DNA array approach to evaluate the ability of DB293 to specifically inhibit transcription factors DNA-binding in a single-step, competitive mode. DB293 inhibits two POU-domain transcription factors Pit-1 and Brn-3 but not IRF-1, despite the presence of an ATGA and AT-rich sites within all three consensus sequences. EMSA, DNase I footprinting and surface-plasmon-resonance experiments determined the precise binding site, affinity and stoichiometry of DB293 interaction to the consensus targets. Binding of DB293 occurred as a cooperative dimer on the ATGA part of Brn-3 site but as two monomers on AT-rich sites of IRF-1 sequence. For Pit-1 site, ATGA or AT-rich mutated sequences identified the contribution of both sites for DB293 recognition. In conclusion, DB293 is a strong inhibitor of two POU-domain transcription factors through a cooperative binding to ATGA. These findings are the first to show that heterocyclic dications can inhibit major groove transcription factors and they open the door to the control of transcription factors activity by those compounds.
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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.