CREB binding protein (CREBBP): Structure-based perspectives for the development of clinical inhibitors

Acetylation is an essential process in biological processes. In tissues, protein acetylation occurs mainly at lysine (K) residues. The balance between acetylation and deacetylation is under the control of two enzyme families, histone acetyltransferase (HAT) and histone deacetylase (HDAC), respectively. Although there are many highly selective and potent HDAC inhibitors (such as romidepsin and belinostat), few HAT inhibitors are undergoing clinical trials. CREBBP, also known as CBP, is a member of the HAT family and plays a key role in several diseases, especially in hematopoietic malignancies, through the modulation of different signaling pathways. Studies have shown that CBP is highly expressed and activated in a variety of different tumors; therefore, its inhibitors have attracted increasing research attention. In this review, we discuss the importance of the structure of CBP in the development of potential inhibitors to provide a reference for the development of new selective CBP inhibitors.