BD2-selective BET inhibitor NUV-868

An orally bioavailable BD2-selective inhibitor of the bromodomain and extra-terminal (BET) family of proteins, with potential antineoplastic activity. Upon oral administration, BD2-selective BET inhibitor NUV-868 primarily targets and binds to the BD2 domain of the BRD4 BET protein, thereby preventing the interaction between BET proteins and acetylated histones. This disrupts chromatin remodeling and suppresses the expression of certain oncogenes, resulting in the inhibition of tumor cell growth. BRD4, a transcriptional regulator, plays an important role in the modulation of gene expression during tumor cellular growth. NUV-868 is designed to be more selective for BD2 than BD1 to avoid the therapeutic limiting toxicities of other non-selective BD1/2 BRD4 inhibitors, such as gastrointestinal (GI) and bone marrow toxicities.