5I8G

CBP in complex with Cpd637 ((R)-4-methyl-6-(1-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-one)

Summary for 5I8G

• Entry DOI: 10.2210/pdb5i8g/pdb
• Descriptor: CREB-binding protein, ZINC ION, (4R)-4-methyl-6-[1-methyl-3-(1-methyl-1H-pyrazol-4-yl)-1H-indazol-5-yl]-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one, ... (8 entities in total)
• Functional Keywords: crebbp, bromodomain, epigenetics, structure-based drug design, transcription-protein binding complex, transcription/protein binding
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q92793
• Total number of polymer chains: 1
• Total formula weight: 32629.97

Authors

Murray, J.M. (deposition date: 2016-02-18, release date: 2016-04-20, Last modification date: 2024-03-06)

Primary citation

Taylor, A.M.,Cote, A.,Hewitt, M.C.,Pastor, R.,Leblanc, Y.,Nasveschuk, C.G.,Romero, F.A.,Crawford, T.D.,Cantone, N.,Jayaram, H.,Setser, J.,Murray, J.,Beresini, M.H.,de Leon Boenig, G.,Chen, Z.,Conery, A.R.,Cummings, R.T.,Dakin, L.A.,Flynn, E.M.,Huang, O.W.,Kaufman, S.,Keller, P.J.,Kiefer, J.R.,Lai, T.,Li, Y.,Liao, J.,Liu, W.,Lu, H.,Pardo, E.,Tsui, V.,Wang, J.,Wang, Y.,Xu, Z.,Yan, F.,Yu, D.,Zawadzke, L.,Zhu, X.,Zhu, X.,Sims, R.J.,Cochran, A.G.,Bellon, S.,Audia, J.E.,Magnuson, S.,Albrecht, B.K.
Fragment-Based Discovery of a Selective and Cell-Active Benzodiazepinone CBP/EP300 Bromodomain Inhibitor (CPI-637).
Acs Med.Chem.Lett., 7:531-536, 2016

PubMed Abstract: CBP and EP300 are highly homologous, bromodomain-containing transcription coactivators involved in numerous cellular pathways relevant to oncology. As part of our effort to explore the potential therapeutic implications of selectively targeting bromodomains, we set out to identify a CBP/EP300 bromodomain inhibitor that was potent both in vitro and in cellular target engagement assays and was selective over the other members of the bromodomain family. Reported here is a series of cell-potent and selective probes of the CBP/EP300 bromodomains, derived from the fragment screening hit 4-methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-one.

PubMed: 27190605
DOI: 10.1021/acsmedchemlett.6b00075

Experimental method

X-RAY DIFFRACTION (1.41 Å)