7YMG

Crystal structure of BRD4 bromodomain 1 (BD1) in complex with 2-({3-ethyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl}amino)-3-(1H-indol-3-yl)propan-1-ol

Summary for 7YMG

• Entry DOI: 10.2210/pdb7ymg/pdb
• Descriptor: Bromodomain-containing protein 4, SODIUM ION, (2S)-2-[(3-ethyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)amino]-3-(1H-indol-3-yl)propan-1-ol, ... (6 entities in total)
• Functional Keywords: brd4, bet inhibitor, complex, transcription
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 30999.40

Authors

Kim, J.H.,Lee, B.I. (deposition date: 2022-07-28, release date: 2023-01-18, Last modification date: 2023-11-29)

Primary citation

Kim, J.H.,Pandit, N.,Yoo, M.,Park, T.H.,Choi, J.U.,Park, C.H.,Jung, K.Y.,Lee, B.I.
Crystal structure of [1,2,4]triazolo[4,3-b]pyridazine derivatives as BRD4 bromodomain inhibitors and structure-activity relationship study.
Sci Rep, 13:10805-10805, 2023

PubMed Abstract: BRD4 contains two tandem bromodomains (BD1 and BD2) that recognize acetylated lysine for epigenetic reading, and these bromodomains are promising therapeutic targets for treating various diseases, including cancers. BRD4 is a well-studied target, and many chemical scaffolds for inhibitors have been developed. Research on the development of BRD4 inhibitors against various diseases is actively being conducted. Herein, we propose a series of [1,2,4]triazolo[4,3-b]pyridazine derivatives as bromodomain inhibitors with micromolar IC values. We characterized the binding modes by determining the crystal structures of BD1 in complex with four selected inhibitors. Compounds containing [1,2,4] triazolo[4,3-b]pyridazine derivatives offer promising starting molecules for designing potent BRD4 BD inhibitors.

PubMed: 37402749
DOI: 10.1038/s41598-023-37527-w

Experimental method

X-RAY DIFFRACTION (1.4 Å)