Definition

An orally bioavailable inhibitor of the bromodomains (BRDs) of the bromodomain and extra-terminal (BET) family of proteins and the histone acetyltransferase (HAT) paralogs CREB binding protein (CBP) and p300 (E1A-associated protein p300; p300 HAT), with potential antineoplastic activity. Upon oral administration, BET/CBP/p300 inhibitor EP31670 targets and binds to the BET proteins bromodomain-containing proteins 2, 3, and 4 (BRD2, BRD3, and BRD4) and bromodomain testis-specific protein (BRDT), as well as the BRD of CBP and p300. This prevents the interaction between BET proteins and acetylated histones, disrupts chromatin remodeling and suppresses the expression of certain oncogenes, resulting in the inhibition of tumor cell growth. BET proteins are transcriptional regulators that play an important role in the modulation of gene expression during cellular growth and development. In addition, this prevents the co-activation of the androgen receptor (AR) including AR-v7 by CBP and p300, which may inhibit tumor cell proliferation in AR-positive tumor cells. The HAT paralogs CBP and p300 are key transcriptional co-activators that are essential for a multitude of cellular processes and are implicated in the progression and therapeutic resistance of certain cancers.