National Center for
5FE9: Crystal Structure Of Human Pcaf Bromodomain In Complex With Compound Sl1122 (compound 13)
Structure-Based Identification of Inhibitory Fragments Targeting the p300/CBP-Associated Factor Bromodomain
J. Med. Chem. (2016) 59 p.1648-1653
The P300/CBP-associated factor plays a central role in retroviral infection and cancer development, and the C-terminal bromodomain provides an opportunity for selective targeting. Here, we report several new classes of acetyl-lysine mimetic ligands ranging from mM to low micromolar affinity that were identified using fragment screening approaches. The binding modes of the most attractive fragments were determined using high resolution crystal structures providing chemical starting points and structural models for the development of potent and selective PCAF inhibitors.