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Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma.

GSE283602 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2026/02/05 Platform GPL28038
At a glance

RNA-seq (gene expression) · human · 12 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
Homo sapiens (human)
Topic
OsteosarcomaThis series is part of our curated briefing on it.
Samples
12 samples: 3 × HOS DMSO 24h, vs 3 × HOS NXP800 24h, vs 3 × HOS DMSO 6h, vs 3 × HOS NXP800 6h,Groups 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
Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcomaCell death discovery · 2026
Summary (written by the submitters)
Osteosarcoma (OS) is the most common primary malignant bone tumor mainly affecting children and young adults. Despite current treatments combining polychemotherapy and surgery, survival rates have remained unchanged for decades, highlighting the need to identify novel therapeutic approaches. NXP800, a newly developed orally available molecule, represents a promising therapeutic option.
Read the full summary ↓
The therapeutic efficacy of NXP800 was evaluated in vitro and in a preclinical murine xenograft model of OS. RNA-seq analysis and functional assays were conducted to investigate the mechanisms of action and molecular target of NXP800. NXP800 decreases the viability of OS cell lines by blocking proliferation and inducing apoptosis. Mechanistically, NXP800 activates the Unfolded Protein Response (UPR), as demonstrated by eIF2α phosphorylation and ATF4 upregulation. This effect is mediated through the engagement of the Integrated Stress Response (ISR) via the activation of GCN2 kinase. Inhibition of GCN2, either through molecular or pharmacological approaches, abolishes NXP800-induced eIF2α phosphorylation and partially restores OS cell viability. Furthermore, NXP800 activates the IRE1α/JNK/c-Jun pathway while increasing the expression of the pro-apoptotic protein Puma. Finally, NXP800 delays tumor growth in preclinical OS model by promoting apoptosis. This study is a preclinical proof-of-principle of therapeutic efficacy of NXP800 both in vitro and in vivo, highlighting the relevance of targeting GCN2, and consequently activating the ISR and UPR, to induce apoptosis and inhibit tumor progression in OS.
Published in
Activating GCN2 and subsequently the Unfolded Protein Response with the small oral molecule NXP800 delays tumor growth in osteosarcoma
Racineau E, Lallier M, Postec A et al. · Cell death discovery 2026 · PMID 41644942 · doi:10.1038/s41420-026-02941-2
This dataset
Open GSE283602 in finder → Find more human RNA-seq datasets → Osteosarcoma landscape →
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 GSE283602_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 PRJNA1194601 and SRA study SRP549655. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41644942) ↗
Study design
3 × HOS DMSO 24h, vs 3 × HOS NXP800 24h, vs 3 × HOS DMSO 6h, vs 3 × HOS NXP800 6h,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
More Osteosarcoma datasets

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