Loading
PDBj
MenuPDBj@FacebookPDBj@X(formerly Twitter)PDBj@BlueSkyPDBj@YouTubewwPDB FoundationwwPDBDonate
RCSB PDBPDBeBMRBAdv. SearchSearch help

5W0E

CREBBP bromodomain in complex with Cpd19 (3-(7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-N-methyl-1-(tetrahydro-2H-pyran-4-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide)

Summary for 5W0E
Entry DOI10.2210/pdb5w0e/pdb
Related5VZS
DescriptorCREB-binding protein, 3-[7-(difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl]-N-methyl-1-(oxan-4-yl)-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide (3 entities in total)
Functional Keywordscrebbp, bromodomain, small molecule inhibitor, transcription regulator-inhibitor complex, transcription regulator/inhibitor
Biological sourceHomo sapiens (Human)
Cellular locationCytoplasm: Q92793
Total number of polymer chains1
Total formula weight18155.57
Authors
Murray, J.M. (deposition date: 2017-05-30, release date: 2018-02-21, Last modification date: 2023-10-04)
Primary citationBronner, S.M.,Murray, J.,Romero, F.A.,Lai, K.W.,Tsui, V.,Cyr, P.,Beresini, M.H.,de Leon Boenig, G.,Chen, Z.,Choo, E.F.,Clark, K.R.,Crawford, T.D.,Jayaram, H.,Kaufman, S.,Li, R.,Li, Y.,Liao, J.,Liang, X.,Liu, W.,Ly, J.,Maher, J.,Wai, J.,Wang, F.,Zheng, A.,Zhu, X.,Magnuson, S.
A Unique Approach to Design Potent and Selective Cyclic Adenosine Monophosphate Response Element Binding Protein, Binding Protein (CBP) Inhibitors.
J. Med. Chem., 60:10151-10171, 2017
Cited by
PubMed Abstract: The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we disclosed the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region and then building into the LPF shelf. Herein, we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family.
PubMed: 29155580
DOI: 10.1021/acs.jmedchem.7b01372
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.41 Å)
Structure validation

229183

PDB entries from 2024-12-18

PDB statisticsPDBj update infoContact PDBjnumon