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Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827

GSE290022 Mus musculus (mouse) RNA-seq (gene expression) 64 samples Submitted 2025/07/28 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 64 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
64 samples: 8 conditions, mostly with about 8 replicates eachGroups are read from the sample names, not from the paper. Check the list below.
Data you can get
A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper
Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827Science advances · 2025
Summary (written by the submitters)
Inhibition of AMP-activated protein kinase (AMPK) is increasingly being explored for its therapeutic potential in some diseases, including certain types of cancers. However, AMPK-inhibitory tool compounds have largely been limited to compound C/dorsomorphin and SBI-0206965, both of which display numerous off-target effects and blocking AMPK-independent metabolic processes.
Read the full summary ↓
Here we describe molecular insights and cellular actions/utility of a recently identified potent AMPK inhibitor BAY-3827. Sequence analysis of highly/lowly-inhibited kinases by BAY-3827, based on in vitro kinase selectivity profiling, predicted key conserved residues involved in the compound-inhibitory effect. A co-crystal structure of the AMPK kinase domain (KD)-BAY-3827 complex resolved at 2.5 Å in comparison with previously reported KD-inhibitor structures, revealed an overlapping binding site in the ATP-binding pocket and common αC helix-out conformations. We identified distinct features of BAY-3827-bound structure which involve a disulfide bridge between αD helix Cys106 and activation loop residue Cys174. This may help to stabilize AMPK conformation upon BAY-3827 binding, where the position of activation loop Asn162 leads the DFG motif Phe158 to adopt a conformation facing the C-terminal kinase lobe displacing His137, leading to a broken regulatory spine and an inactive kinase state. BAY-3827 at 2.5-5 μM, but not structurally resembling inactive BAY-974, fully blocked AMPK activator (MK-8722)-mediated phosphorylation of ACC1 and inhibition of lipogenesis in hepatocytes. Unbiased transcriptome analysis in MK-8722-treated wild-type and AMPK-null hepatocytes revealed that >30% of MK-8722-stimulated AMPK-dependent genes could be downregulated by 5 μM BAY-3827. Based on its greater selectivity and potency substantiated by comprehensive molecular/cellular investigations. BAY-3827 is a powerful tool to delineate AMPK functions.
Published in
Mechanism and cellular actions of the potent AMPK inhibitor BAY-3827
Fraguas Bringas C, Ahangar MS, Cuenco J et al. · Science advances 2025 · PMID 40845097 · doi:10.1126/sciadv.adx2434
This dataset
Open GSE290022 in finder → Find more mouse RNA-seq datasets →
Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓
2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE290022_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓
3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1225752 and SRA study SRP565082. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40845097) ↗
Study design
8 conditions, mostly with about 8 replicates each
WT_DMSO ×8 WT_MK-8722 ×8 WT_BAY ×8 WT_BAY+MK-8722 ×8 KO_DMSO ×8 KO_MK-8722 ×8 KO_BAY ×8 KO_BAY+MK-8722 ×8

Supports a between-group comparison across 64 samples.

How we read this: 8 replicated groups read from 64 sample titles; they account for 64 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

+ 24 more — browse all 64 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.