Targeting twin acetyltransferases p300 and CBP
p300 and CBP are paralogue (twin) histone acetyltransferases (HATs) that impact the expression of cancer driving genes, as well as key cancer-related signalling pathways.
The function of p300/CBP can be inhibited by specific small molecules binding into pockets on the surface of the proteins. CellCentric has focused on targeting the bromodomain pocket. Binding into here affects p300/CBP’s ability to act as transcription co-activation factors of cancer associated genes such as MYC and IRF4.
p300/CBP inhibition additionally prevents the acetylation of important signalling proteins, which means they can then be ubiquitinylated instead, and turned over/destroyed through proteosomal degradation.