7TD9

G-059 bound to the SMARCA4 (BRG1) Bromodomain

This is a non-PDB format compatible entry.

Summary for 7TD9

• Entry DOI: 10.2210/pdb7td9/pdb
• Related: 7TAB
• Descriptor: Isoform 4 of Transcription activator BRG1, 4-phenyl-5H-pyridazino[4,3-b]indol-3-amine (3 entities in total)
• Functional Keywords: bromodomain brg1 smarca4 inhibitor, protein binding, hydrolase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 3
• Total formula weight: 46093.57

Authors

Tang, Y.,Poy, F.,Taylor, A.M.,Cochran, A.G.,Bellon, S.F. (deposition date: 2021-12-30, release date: 2022-08-17, Last modification date: 2023-10-18)

Primary citation

Taylor, A.M.,Bailey, C.,Belmont, L.D.,Campbell, R.,Cantone, N.,Cote, A.,Crawford, T.D.,Cummings, R.,DeMent, K.,Duplessis, M.,Flynn, M.,Good, A.C.,Huang, H.R.,Joshi, S.,Leblanc, Y.,Murray, J.,Nasveschuk, C.G.,Neiss, A.,Poy, F.,Romero, F.A.,Sandy, P.,Tang, Y.,Tsui, V.,Zawadzke, L.,Sims 3rd, R.J.,Audia, J.E.,Bellon, S.F.,Magnuson, S.R.,Albrecht, B.K.,Cochran, A.G.
GNE-064: A Potent, Selective, and Orally Bioavailable Chemical Probe for the Bromodomains of SMARCA2 and SMARCA4 and the Fifth Bromodomain of PBRM1.
J.Med.Chem., 65:11177-11186, 2022

PubMed Abstract: Bromodomains are acetyllysine recognition domains present in a variety of human proteins. Bromodomains also bind small molecules that compete with acetyllysine, and therefore bromodomains have been targets for drug discovery efforts. Highly potent and selective ligands with good cellular permeability have been proposed as chemical probes for use in exploring the functions of many of the bromodomain proteins. We report here the discovery of a class of such inhibitors targeting the family VIII bromodomains of SMARCA2 (BRM) and SMARCA4 (BRG1), and PBRM1 (polybromo-1) bromodomain 5. We propose one example from this series, GNE-064, as a chemical probe for the bromodomains SMARCA2, SMARCA4, and PBRM1(5) with the potential for use.

PubMed: 35930799
DOI: 10.1021/acs.jmedchem.2c00662

Experimental method

X-RAY DIFFRACTION (1.61 Å)