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An orally active dual CBP/p300 degrader targets core dependencies of multiple myeloma [ATAC-seq]

GSE318521 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 24 samples Submitted 2026/05/14 Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 24 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)
Topic
Multiple myelomaThis series is part of our curated briefing on it.
Samples
24 samples: 6 conditions, mostly with about 4 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.
Summary (written by the submitters)
The enhancer lysine acetyltransferases CBP and p300 are compelling targets for multiple myeloma therapy. Chemical inhibition of these multidomain factors, either through the bromodomain or the catalytic acetyltransferase domain, show promising activity in pre-clinical models of myeloma and other cancers. Some compounds, including the CBP/p300 bromodomain inhibitor inobrodib, have progressed to early-stage clinical trials.
Read the full summary ↓
Chemical degradation of CBP/p300 is the only modality that can completely disrupt all functional domains of CBP and p300. Our previous attempts to induce CBP/p300 targeted degradation led to dCBP-1, a potent tool compound that induces degradation of both CBP and p300 by hijacking the activity of the E3 ligase CRBN. Here we comprehensively demonstrate across a large panel of cell lines how CBP/p300 degradation compares to inhibition, with pronounced selective antiproliferative activity towards multiple myeloma cells. We use chemical linker optimization strategies to create a compound with better pharmacokinetic properties to enable use in animal models. Through these efforts we define an advanced analog of dCBP-1, dCBP-30, that has improved potency in vitro, along with improved in vivo properties including oral bioavailability. dCBP-30 led to potent and sustained loss of CBP and p300 in myeloma cell lines, potent inhibition of several myeloma-specific dependency programs, and elicits tumor reduction in xenograft models as a single agent and in combination with dexamethasone when delivered orally.
This dataset
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.

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 GSE318521_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1419157 and SRA study SRP674837. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 4 replicates each
MM1S, DMSO, 24h, ×4 MM1S, DMSO, 6h, ×4 MM1S, DMSO, 2h, ×4 MM1S, dCBP30, 24h, ×4 MM1S, dCBP30, 6h, ×4 MM1S, dCBP30, 2h, ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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 Multiple myeloma datasets

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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.