1644598-66-2Relevant academic research and scientific papers
Controlling Intramolecular Interactions in the Design of Selective, High-Affinity Ligands for the CREBBP Bromodomain
Brand, Michael,Clayton, James,Moroglu, Mustafa,Schiedel, Matthias,Picaud, Sarah,Bluck, Joseph P.,Skwarska, Anna,Bolland, Hannah,Chan, Anthony K. N.,Laurin, Corentine M. C.,Scorah, Amy R.,See, Larissa,Rooney, Timothy P. C.,Andrews, Katrina H.,Fedorov, Oleg,Perell, Gabriella,Kalra, Prakriti,Vinh, Kayla B.,Cortopassi, Wilian A.,Heitel, Pascal,Christensen, Kirsten E.,Cooper, Richard I.,Paton, Robert S.,Pomerantz, William C. K.,Biggin, Philip C.,Hammond, Ester M.,Filippakopoulos, Panagis,Conway, Stuart J.
, p. 10102 - 10123 (2021/07/31)
CREBBP (CBP/KAT3A) and its paralogue EP300 (KAT3B) are lysine acetyltransferases (KATs) that are essential for human development. They each comprise 10 domains through which they interact with >400 proteins, making them important transcriptional co-activa
Selective Fragments for the CREBBP Bromodomain Identified from an Encoded Self-assembly Chemical Library
Catalano, Marco,Moroglu, Mustafa,Balbi, Petra,Mazzieri, Federica,Clayton, James,Andrews, Katrina H.,Bigatti, Martina,Scheuermann, J?rg,Conway, Stuart J.,Neri, Dario
supporting information, p. 1752 - 1756 (2020/08/21)
DNA-encoded chemical libraries (DECLs) are collections of chemical moieties individually coupled to distinctive DNA barcodes. Compounds can be displayed either at the end of a single DNA strand (i. e., single-pharmacophore libraries) or at the extremities of two complementary DNA strands (i. e., dual-pharmacophore libraries). In this work, we describe the use of a dual-pharmacophore encoded self-assembly chemical (ESAC) library for the affinity maturation of a known 4,5-dihydrobenzodiazepinone ring (THBD) acetyl-lysine (KAc) mimic for the cyclic-AMP response element binding protein (CREB) binding protein (CREBBP or CBP) bromodomain. The new pair of fragments discovered from library selection showed a sub-micromolar affinity for the CREBBP bromodomain in fluorescence polarization and ELISA assays, and selectivity against BRD4(1).
A series of potent crebbp bromodomain ligands reveals an induced-fit pocket stabilized by a cation-π interaction
Rooney, Timothy P. C.,Filippakopoulos, Panagis,Fedorov, Oleg,Picaud, Sarah,Cortopassi, Wilian A.,Hay, Duncan A.,Martin, Sarah,Tumber, Anthony,Rogers, Catherine M.,Philpott, Martin,Wang, Minghua,Thompson, Amber L.,Heightman, Tom D.,Pryde, David C.,Cook, Andrew,Paton, Robert S.,Mueller, Susanne,Knapp, Stefan,Brennan, Paul E.,Conway, Stuart J.
supporting information, p. 6126 - 6130 (2014/06/23)
The benzoxazinone and dihydroquinoxalinone fragments were employed as novel acetyl lysine mimics in the development of CREBBP bromodomain ligands. While the benzoxazinone series showed low affinity for the CREBBP bromodomain, expansion of the dihydroquino
