ArticleTargeted oncology2023
FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer.
Article in Targeted oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- From EGFR PTM network to TKI resistance: spatial subtypes and targeting in lung cancer.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Dendritic cells: understanding ontogeny, subsets, functions, and their clinical applications.Molecular biomedicine · 2025Review
- Advances of androgen receptor in triple-negative breast cancer: from molecular mechanisms to clinical applications.Discover oncology · 2025Review
- NAA10 (N-Alpha-Acetyltransferase 10): A Multifunctional Regulator in Development, Disease, and Cancer.Cells · 2025Review
- Histone acetylation modulators in breast cancer.Breast cancer research : BCR · 2025Review
- A narrative review of epigenetic marker in H3K27ac and its emerging potential as a therapeutic target in cancer.Epigenomics · 2025Review
- Review
- The important role of the histone acetyltransferases p300/CBP in cancer and the promising anticancer effects of p300/CBP inhibitors.Cell biology and toxicology · 2025Review
- Genetic dysregulation of EP300 in cancers in light of cancer epigenome control - targeting of p300-proficient and -deficient cancers.Molecular therapy. Oncology · 2024Review
- Regulatory mechanisms of steroid hormone receptors on gene transcription through chromatin interaction and enhancer reprogramming.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.Cellular & molecular biology letters · 2024Review
- CREB-binding protein/P300 bromodomain inhibition reduces neutrophil accumulation and activates antitumor immunity in triple-negative breast cancer.JCI insight · 2024Article
- CBP/P300 BRD Inhibition Reduces Neutrophil Accumulation and Activates Antitumor Immunity in TNBC.bioRxiv : the preprint server for biology · 2024Article
- Androgen Receptor-Interacting Proteins in Prostate Cancer Development and Therapy Resistance.The American journal of pathology · 2024Review
- Review
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Comparative Analysis of Drug-like EP300/CREBBP Acetyltransferase Inhibitors.ACS chemical biology · 2023Article
- Comparative analysis of drug-like EP300/CREBBP acetyltransferase inhibitors.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPatients with triple-negative breast cancer (TNBC) expressing the androgen receptor (AR) respond poorly to neoadjuvant chemotherapy, although AR antagonists have shown promising clinical activity, suggesting these tumors are AR-dependent. cAMP responsive element binding protein (CREB)-binding protein (CBP) and p300 are transcriptional co-activators for the AR, a key driver of AR+ breast and prostate cancer, and may provide a novel therapeutic target in AR+ TNBC.
objectivesThe aim of this study was to determine the therapeutic potential of FT-6876, a new CBP/p300 bromodomain inhibitor, in breast cancer models with a range of AR levels in vitro and in vivo.
methodsEffects of FT-6876 on the CBP/p300 pathway were determined by combining chromatin immunoprecipitation (ChIP) with precision run-on sequencing (PRO-seq) complemented with H3K27 acetylation (Ac) and transcriptional profiling. The antiproliferative effect of FT-6876 was also measured in vitro and in vivo.
resultsWe describe the discovery of FT-6876, a potent and selective CBP/p300 bromodomain inhibitor. The combination of ChIP and PRO-seq confirmed the reduction in H3K27Ac at specific promoter sites concurrent with a decrease in CBP/p300 on the chromatin and a reduction in nascent RNA and enhancer RNA. This was associated with a time- and concentration-dependent reduction in H3K37Ac associated with a decrease in AR and estrogen receptor (ER) target gene expression. This led to a time-dependent growth inhibition in AR+ models, correlated with AR expression. Tumor growth inhibition was also observed in AR+ tumor models of TNBC and ER+ breast cancer subtypes with consistent pharmacokinetics and pharmacodynamics.
conclusionOur findings demonstrate FT-6876 as a promising new CBP/p300 bromodomain inhibitor, with efficacy in preclinical models of AR+ breast cancer.
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