GEO series

Efficient in vivo pharmacological inhibition of ∆FOSB with YL-0441 in brain

GSE319820 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 38 samples Submitted 2026/07/01 Platform GPL21103

Summary

ΔFOSB, an unusually stable member of the AP-1family of transcription factors, mediates long-term maladaptationsthat play a key role in the pathogenesis of drug addiction, cognitive decline, dyskinesias, and several other chronic neurological and psychiatric conditions. We have recently identified that 2-phenoxybenzenesulfonic acid-containing compounds disrupt the binding of ΔFOSB to DNA in vitroin cell-based assays. We show that one such analog, YL0441, disrupts the binding of ΔFOSB to DNA in vitroand in vivo, and suppresses ΔFOSB-function in cell-based assays. Importantly, infusion of YL0441 into the hippocampus of APP mice (a mouse model for Alzheimer's diseaseneuropathology) leads to virtually complete loss of ΔFOSB bound to genomic DNA as detected by CUT&RUN sequencing. Our findings corroborate that the binding/release of AP1 transcription factors to DNA can be controlled via small moleculesin vivo, even by analogs of a compound that binds to a groove outside of the DNA-binding cleft, and that our lead can be optimized via medicinal chemistry to yield a much moreefficacious inhibitor of ΔFOSB function in vivo. These findings define a strategy to design small-molecule inhibitors for other AP-1and AP-1-related transcription factors, in particular, those involved in neuropsychiatric and neurological disorders.

Published in

Efficient In Vivo Pharmacological Inhibition of ΔFOSB, an AP-1 Transcription Factor, in the Brain

McNeme S, Kumar A, Yim YY et al. · ACS chemical neuroscience 2026 · PMID 41817117 · doi:10.1021/acschemneuro.5c00890

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Direct links to NCBI, no account and no request form: the whole study as GSE319820_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 38 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1425140 and SRA study SRP677896. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41817117) ↗

Study design

38 conditions, each sampled once — no replicated groups

Read from 38 sample titles: 38 distinct titles with little repetition. Check it against the sample list below before relying on it.

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