CREB-binding protein (CBP) and E1A-associated protein p300 are transcriptional co-activators that modulate DNA replication, DNA repair, cell growth, transformation, and development.1,2 Both CBP and p300 contain bromodomains, which mediate their binding to acetylated lysine residues on histones and other proteins.3 PF-CBP1 is an inhibitor of the CBP and p300 bromodomains (IC50s = 125 and 363 nM, respectively).4 It displays greater than 100-fold selectivity for the bromodomain of CBP over those of BRD4 and a panel of other proteins.4 PF-CBP1 reduces the expression of inflammatory cytokines by LPS-stimulated primary macrophages.4 It also suppresses the expression of RGS4 (regulator of G protein signaling 4) in primary cortical neurons.4
1.Iyer, N.G., ?zdag, H., and Caldas, C.p300/CBP and cancerOncogene234225-4231(2004) 2.Kalkhoven, E.CBP and p300: HATs for different occasionsBiochem. Pharmacol.681145-1155(2004) 3.Zeng, L., Zhang, Q., Gerona-Navarro, G., et al.Structural basis of site-specific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300Structure16(4)643-652(2008) 4.Piatnitski Chekler, E.L., Pellegrino, J.A., Lanz, T.A., et al.Transcriptional profiling of a selective CREB binding protein bromodomain inhibitor highlights therapeutic opportunitiesChem. Biol.22(12)1588-1596(2015)