GEO series
An orally active dual CBP/p300 degrader targets core dependencies of multiple myeloma [ATAC-seq]
GSE318521
Homo sapiens
Genome binding/occupancy profiling by high throughput sequencing
24 samples
Submitted 2026/05/14
Platform GPL24676
Summary
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. 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
Direct links to NCBI, no account and no request form: the whole study as GSE318521_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 24 samples. Raw sequencing reads are also available from 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.
6 replicated groups read from 24 sample titles; they account for 24 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9497034 MM1S, DMSO, 24h, rep1
- GSM9497035 MM1S, DMSO, 24h, rep2
- GSM9497036 MM1S, DMSO, 24h, rep3
- GSM9497037 MM1S, DMSO, 24h, rep4
- GSM9497038 MM1S, DMSO, 6h, rep1
- GSM9497039 MM1S, DMSO, 6h, rep2
- GSM9497040 MM1S, DMSO, 6h, rep3
- GSM9497041 MM1S, DMSO, 6h, rep4
- GSM9497042 MM1S, DMSO, 2h, rep1
- GSM9497043 MM1S, DMSO, 2h, rep2
- GSM9497044 MM1S, DMSO, 2h, rep3
- GSM9497045 MM1S, DMSO, 2h, rep4
- GSM9497046 MM1S, dCBP30, 24h, rep1
- GSM9497047 MM1S, dCBP30, 24h, rep2
- GSM9497048 MM1S, dCBP30, 24h, rep3
- GSM9497049 MM1S, dCBP30, 24h, rep4
- GSM9497050 MM1S, dCBP30, 6h, rep1
- GSM9497051 MM1S, dCBP30, 6h, rep2
- GSM9497052 MM1S, dCBP30, 6h, rep3
- GSM9497053 MM1S, dCBP30, 6h, rep4
- GSM9497054 MM1S, dCBP30, 2h, rep1
- GSM9497055 MM1S, dCBP30, 2h, rep2
- GSM9497056 MM1S, dCBP30, 2h, rep3
- GSM9497057 MM1S, dCBP30, 2h, rep4
Similar datasets
- GSE294275 Transcriptional analysis of direct NSD2 target genes in t(4;14) multiple myeloma reveals H3K36me2-dependent regulation and H3K27me3 antagonism [CUT&TAG] 40 samples
- GSE303343 A unified network systems approach uncovers a core program underlying T follicular helper cell differentiation [CUT&RUN] 48 samples
- GSE282258 Imaging-based drug screening combined with moleuclar profiling identifies signatures and drivers of therapy resistance in pediatric AML [ATAC-seq] 44 samples
- GSE334112 Reversible epiblast regionalisation determines differentiation potential of human PSCs [ATAC-seq] 38 samples
- GSE316389 Chromatin accessibility and gene expression profiling of primary and metastatic ER+ breast cancer [ATAC-seq] 36 samples
- GSE280280 Reprogramming of Cellular Plasticity via ETS and MYC Core-regulatory circuits During Response to MAPK Inhibition in BRAF-mutant colorectal cancer 36 samples
- GSE288843 Multiomic assessments of LNCaP and derived cell strains reveal determinants of prostate cancer pathobiology (ATAC-Seq) 30 samples
- GSE267470 Dual targeting of processive transcription for Myc-driven circuitry in medulloblastoma [CUT&RUN] 12 samples
Share this dataset
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.