ArticleChemistryOpen2016
A Multi-target Small Molecule for Targeted Transcriptional Activation of Therapeutically Significant Nervous System Genes.
Article in ChemistryOpen, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Modulating DNA by polyamides to regulate transcription factor PU.1-DNA binding interactions.Biochimie · 2019Article
- Synthetic DNA-Binding Inhibitor of HES1 Alters the Notch Signaling Pathway and Induces Neuronal Differentiation.ACS omega · 2018Article
- A synthetic DNA-binding inhibitor of SOX2 guides human induced pluripotent stem cells to differentiate into mesoderm.Nucleic acids research · 2017Article
- A Multi-target Small Molecule for Targeted Transcriptional Activation of Therapeutically Significant Nervous System Genes.ChemistryOpen · 2016Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An integrated multi-target small molecule capable of altering dynamic epigenetic and transcription programs associated with the brain and nervous system has versatile applications in the regulation of therapeutic and cell-fate genes. Recently, we have been constructing targeted epigenetic ON switches by integrating sequence-specific DNA binding pyrrole-imidazole polyamides with a potent histone deacetylase inhibitor SAHA. Here, we identified a DNA-based epigenetic ON switch termed SAHA-L as the first-ever multi-target small molecule capable of inducing transcription programs associated with the human neural system and brain synapses networks in BJ human foreskin fibroblasts and 201B7-iPS cells. Ingenuity pathway analysis showed that SAHA-L activates the signaling of synaptic receptors like glutamate and γ-aminobutyric acid, which are key components of autism spectrum disorders. The long-term incubation of SAHA-L in 201B7-iPS cells induced morphology changes and promoted a neural progenitor state. Our finding suggests that the tunable SAHA-L could be advanced as a cell-type-independent multi-target small molecule for therapeutic and/or cell-fate gene modulation.
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Registered trials
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