ArticleBiochemistry2019
Combination Targeting of the Bromodomain and Acetyltransferase Active Site of p300/CBP.
Article in Biochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Histone modification cross-talk: analytical tools and molecular mechanisms.The Biochemical journal · 2026Review
- Targeting histone H2B acetylated enhanceosomes via p300/CBP degradation in prostate cancer.Nature genetics · 2025Article
- Review
- Selective CBP/EP300 Bromodomain Inhibitors: Novel Epigenetic Tools to Counter TNF-α-Driven Inflammation.JACS Au · 2025Article
- Development of C646-Based Proteolysis Targeting Chimeras Degraders of the Lysine Acetyltransferases CBP and p300.ChemMedChem · 2025Article
- Targeting lysine acetylation readers and writers.Nature reviews. Drug discovery · 2025Review
- 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
- Aberrant histone modifications in pediatric brain tumors.Frontiers in oncology · 2025Review
- Targeting the epigenome and tumor heterogeneity: advances in immunotherapy for chemoresistant metastatic colorectal cancer.Frontiers in immunology · 2025Review
- Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.Nature communications · 2024Article
- EP300/CREBBP acetyltransferase inhibition limits steroid receptor and FOXA1 signaling in prostate cancer cells.Cellular and molecular life sciences : CMLS · 2024Article
- Discovery and Characterization of Active CBP/EP300 Degraders Targeting the HAT Domain.ACS medicinal chemistry letters · 2024Article
- EP300 as a Molecular Integrator of Fibrotic Transcriptional Programs.International journal of molecular sciences · 2023Review
- Molecular Targeted Therapies in Metastatic Prostate Cancer: Recent Advances and Future Challenges.Cancers · 2023Review
- FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer.Targeted oncology · 2023Article
- KATs off: Biomedical insights from lysine acetyltransferase inhibitors.Current opinion in chemical biology · 2023Review
- TAZ/YAP fusion proteins: mechanistic insights and therapeutic opportunities.Trends in cancer · 2022Review
- TRPM3-Induced Gene Transcription Is under Epigenetic Control.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Report of the First International Symposium on NUT Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Targeting CDCP1 gene transcription coactivated by BRD4 and CBP/p300 in castration-resistant prostate cancer.Oncogene · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
p300 and CBP are highly related histone acetyltransferase (HAT) enzymes that regulate gene expression, and their dysregulation has been linked to cancer and other diseases. p300/CBP is composed of a number of domains including a HAT domain, which is inhibited by the small molecule A-485, and an acetyl-lysine binding bromodomain, which was recently found to be selectively antagonized by the small molecule I-CBP112. Here we show that the combination of I-CBP112 and A-485 can synergize to inhibit prostate cancer cell proliferation. We find that the combination confers a dramatic reduction in p300 chromatin occupancy compared to the individual effects of blocking either domain alone. Accompanying this loss of p300 on chromatin, combination treatment leads to the reduction of specific mRNAs including androgen-dependent and pro-oncogenic prostate genes such as KLK3 (PSA) and c-Myc. Consistent with p300 directly affecting gene expression, mRNAs that are significantly reduced by combination treatment also exhibit a strong reduction in p300 chromatin occupancy at their gene promoters. The relatively few mRNAs that are up-regulated upon combination treatment show no correlation with p300 occupancy. These studies provide support for the pharmacologic advantage of concurrent targeting of two domains within one key epigenetic modification enzyme.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.