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Covalent pan-TEAD inhibitors block YAP activity and demonstrate brain penetrance in Hippo-dependent cancer models [ATAC-seq]

GSE330305 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 30 samples Submitted 2026/05/07 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 30 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
30 samples: 10 conditions, mostly in triplicateGroups 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.
Summary (written by the submitters)
TEAD proteins are a family of transcription factors that enable the oncogenic activity of deregulated Hippo signaling and are a promising therapeutic target in oncology. Targeting the lipid pocket of TEAD is an established path to inhibit the oncogenic activities of the cofactors YAP and TAZ. Here we present two covalent pan-TEAD inhibitors that bind to the lipid pocket, GNE-8025 and GNE-2181.
Read the full summary ↓
GNE-8025 binds TEAD proteins covalently at a conserved cysteine residue to engage the lipid pocket and allosterically disrupt the interaction of TEAD proteins with YAP. GNE-2181 is a further optimized version of GNE-8025 with properties that enable brain penetrance in vivo. Both of these small molecules suppress the proliferation of YAP-driven tumor cells both in vitro and in vivo and increase activity of a broad range of inhibitors of the MAPK pathway. We demonstrate that these molecules have exceptional efficacy in Hippo-driven in vivo tumor models, including in a mouse model of brain metastases where GNE-2181 treatment significantly inhibits the growth of intracranial brain tumors. Altogether we present a next-generation class of TEAD inhibitors. The development of GNE-8025 and GNE-2181 is a significant advancement towards potent, specific, and effective Hippo-targeting cancer therapies.
This dataset
Open GSE330305 in finder → Find more human ChIP / ATAC / CUT&Tag 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 GSE330305_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1463356 and SRA study SRP698473. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
10 conditions, mostly in triplicate
ATAC-seq NCI-H226 xenograft tumor Vehicle ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 0.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 0.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 0.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 0.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 0.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 1.… ×3 ATAC-seq NCI-H226 xenograft tumor GNE-8025 5 … ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 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
Datasets on a similar topic

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