4LRG

Structure of BRD4 bromodomain 1 with a dimethyl thiophene isoxazole azepine carboxamide

Summary for 4LRG

• Entry DOI: 10.2210/pdb4lrg/pdb
• Related: 4LR6
• Descriptor: Bromodomain-containing protein 4, 2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-[1,2]oxazolo[5,4-c]thieno[2,3-e]azepin-6-yl]acetamide (3 entities in total)
• Functional Keywords: bet inhibitor, brd4 first bromodomain, transcription regulator-inhibitor complex, transcription regulator/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O60885
• Total number of polymer chains: 1
• Total formula weight: 15526.23

Authors

Ravichandran, S.,Jayaram, H.,Poy, F.,Gehling, V.,Hewitt, M.,Vaswani, R.,Leblanc, Y.,Cote, A.,Nasveschuk, C.,Taylor, A.,Harmange, J.-C.,Audia, J.,Pardo, E.,Joshi, S.,Sandy, P.,Mertz, J.,Sims, R.,Bergeron, L.,Bryant, B.,Yellapuntala, S.,Nandana, B.S.,Birudukota, S.,Albrecht, B.,Bellon, S. (deposition date: 2013-07-19, release date: 2013-08-07, Last modification date: 2024-02-28)

Primary citation

Gehling, V.S.,Hewitt, M.C.,Vaswani, R.G.,Leblanc, Y.,Cote, A.,Nasveschuk, C.G.,Taylor, A.M.,Harmange, J.C.,Audia, J.E.,Pardo, E.,Joshi, S.,Sandy, P.,Mertz, J.A.,Sims, R.J.,Bergeron, L.,Bryant, B.M.,Bellon, S.,Poy, F.,Jayaram, H.,Sankaranarayanan, R.,Yellapantula, S.,Bangalore Srinivasamurthy, N.,Birudukota, S.,Albrecht, B.K.
Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors.
ACS Med Chem Lett, 4:835-840, 2013

PubMed Abstract: The identification of a novel series of small molecule BET inhibitors is described. Using crystallographic binding modes of an amino-isoxazole fragment and known BET inhibitors, a structure-based drug design effort lead to a novel isoxazole azepine scaffold. This scaffold showed good potency in biochemical and cellular assays and oral activity in an in vivo model of BET inhibition.

PubMed: 24900758
DOI: 10.1021/ml4001485

Experimental method

X-RAY DIFFRACTION (2.21 Å)