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Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 in vitro by Rezatapopt (PC14586), a Small Molecule Reactivator [in vitro]

GSE276223 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2025/02/03 Platform GPL20795
At a glance

RNA-seq (gene expression) · human · 48 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)
Samples
48 samples: 16 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.
Paper
Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule ReactivatorCancer discovery · 2025
Summary (written by the submitters)
Restoration of the tumor suppressor function of tumor-associated p53 mutants, including tumors harboring the TP53 Y220C mutation, has posed a significant challenge and remains an attractive target for therapeutic discovery. Here, we describe a clinical candidate Rezatapopt (PC14586) designed to stabilize the p53 Y220C mutant protein and restore wild-type (WT) p53 function.
Read the full summary ↓
PC14586 induced global gene expression changes in the cell lines harboring the TP53 Y220C mutation (NUGC-3 and T3M-4) but not in cells lacking p53 Y220C-mutant protein (NUGC-3 KO and SJSA-1). Extensive transcriptomics analysis of cells harboring the TP53 Y220C mutation following PC14586 treatment revealed the induction of p53 direct target genes, including protein-coding genes and long non-coding RNAs (lncRNAs), and repression of cell cycle progression-associated genes in a distinct temporal pattern. Our data demonstrate that PC14586 administration inhibited cell proliferation in vitro via the induction of WT p53 transcriptional signatures, including a sustained transcriptional repression of genes involved in cell cycle regulation. Following these investigations and additional in vivo studies, rezatapopt (PC14586) was identified as a clinical candidate and is currently being evaluated in the registrational Phase 2 PYNNACLE study.
Published in
Restoration of the Tumor Suppressor Function of Y220C-Mutant p53 by Rezatapopt, a Small-Molecule Reactivator
Puzio-Kuter AM, Xu L, McBrayer MK et al. · Cancer discovery 2025 · PMID 39945593 · doi:10.1158/2159-8290.CD-24-1421
This dataset
Open GSE276223 in finder → Find more human 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 GSE276223_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 PRJNA1156010 and SRA study SRP530187. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39945593) ↗
Study design
16 conditions, mostly in triplicate
NUGC-3 cells, DMSO, 5h, ×3 NUGC-3 cells, PC14586, 5h, ×3 T3M-4 cells, DMSO, 5h, ×3 T3M-4 cells, PC14586, 5h, ×3 NUGC-3 KO cells, DMSO, 5h, ×3 NUGC-3 KO cells, PC14586, 5h, ×3 SJSA-1 cells, DMSO, 5h, ×3 SJSA-1 cells, PC14586, 5h, ×3 +8 more

Supports a between-group comparison across 48 samples.

How we read this: 16 replicated groups read from 48 sample titles; they account for 48 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

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