CREB-binding protein and E1A-binding protein p300 bromodomains (CBP/EP300 bromodomains)

CREB-binding protein (CBP) and E1A-binding protein p300 (EP300) are highly homologous transcriptional coactivators that play central roles in regulating gene expression through their histone acetyltransferase (HAT) activity and their ability to act as protein scaffolds [UniProt P45973, Q09472]. The bromodomains of CBP and EP300 are specialized protein modules that recognize and bind to acetylated lysine residues on histone tails and other proteins, facilitating the assembly of transcriptional complexes at specific genomic loci [PubMed: 29474153]. In many cancers, including prostate cancer and various hematological malignancies, the CBP/EP300 bromodomains are exploited to drive the expression of oncogenes such as MYC and the androgen receptor [PubMed: 33009425]. Small molecule inhibitors targeting these bromodomains aim to disrupt these oncogenic signaling pathways by preventing the recruitment of CBP/EP300 to chromatin [PubMed: 31501250]. Clinical development of CBP/EP300 bromodomain inhibitors, such as inobrodib (CCS1477), has shown promise in treating refractory cancers by modulating the epigenetic landscape [ClinicalTrials.gov NCT03568331].

Other names

CREBBP/EP300 bromodomainsp300/CBP bromodomainsKAT3A/KAT3B bromodomainsCBP/p300 BRD

Small-molecule inhibition of the bromodomain, which prevents the recognition of acetylated lysine residues on histones and other proteins, thereby disrupting the recruitment of CBP/EP300 to specific gene enhancers and promoters and inhibiting the transcription of oncogenic drivers [PubMed: 29474153].