A Series of Potent CREBBP Bromodomain Ligands Reveals an Induced-Fit Pocket Stabilized by a Cation–π Interaction (pages 6126–6130)
Timothy P. C. Rooney, Dr. Panagis Filippakopoulos, Dr. Oleg Fedorov, Dr. Sarah Picaud, Wilian A. Cortopassi, Duncan A. Hay, Dr. Sarah Martin, Dr. Anthony Tumber, Dr. Catherine M. Rogers, Dr. Martin Philpott, Dr. Minghua Wang, Dr. Amber L. Thompson, Dr. Tom D. Heightman, Dr. David C. Pryde, Dr. Andrew Cook, Prof. Dr. Robert S. Paton, Dr. Susanne Müller, Prof. Dr. Stefan Knapp, Dr. Paul E. Brennan and Prof. Dr. Stuart J. Conway
Article first published online: 12 MAY 2014 | DOI: 10.1002/anie.201402750
Ligands made to fit: A series of dihydroquinoxalinone fragments were employed as acetyl lysine mimics in the development of CREBBP bromodomain ligands. The side chain of these ligands binds in an induced-fit pocket and forms a cation–π interaction with R1173 of CREBBP. The most potent compound inhibits binding of CREBBP to chromatin in U2OS cells.