CREB-binding protein bromodomain and E1A binding protein p300 bromodomain (CBP bromodomain and p300 bromodomain (CBP-BRD, p300-BRD))

The CBP (CREB-binding protein) and p300 bromodomains are structurally conserved modules within two paralogous lysine acetyltransferases, CREBBP and EP300. These bromodomains specifically recognize and bind acetylated lysine residues, primarily on histone tails, acting as "readers" of the histone code and directing the associated acetyltransferase activity to complementary chromatin regions. This recognition is essential for transcriptional activation, enhancer function, and regulation of critical cellular processes, including proliferation, differentiation, and stress response. Targeting the bromodomains of CBP and p300 has emerged as a strategy for modulating aberrant gene expression in cancer and immune-mediated diseases. Several highly selective small molecule inhibitors (e.g., CBP30, (−)-OXFBD05) disrupt acetyl-lysine recognition, altering transcription and reducing oncogenic signaling, though none have reached clinical approval as of 2024[2][3][6][4].

Other names

p300 bromodomainCBP bromodomainEP300 bromodomainCREBBP bromodomainKAT3A bromodomain (for CBP)KAT3B bromodomain (for p300)K(lysine) acetyltransferase 3A/3B bromodomainBRD family III (for CBP/p300)

Competitive inhibition of the bromodomain pocket, preventing the binding of acetylated lysine residues on histone and non-histone proteins; Modulation of gene transcription by altering chromatin structure and blocking recruitment of transcriptional coactivators; Typically leads to downregulation of oncogenes (e.g., c-Myc) and disruption of Th17-mediated inflammatory pathways