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- Title
Crystal structure of [1,2,4]triazolo[4,3-b]pyridazine derivatives as BRD4 bromodomain inhibitors and structure–activity relationship study.
- Authors
Kim, Jung-Hoon; Pandit, Navin; Yoo, Miyoun; Park, Tae Hyun; Choi, Ji U; Park, Chi Hoon; Jung, Kwan-Young; Lee, Byung Il
- 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 IC50 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.
- Subjects
STRUCTURE-activity relationships; CRYSTAL structure; CHEMICAL inhibitors; PYRIDAZINES; DRUG target; LYSINE
- Publication
Scientific Reports, 2023, Vol 13, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-023-37527-w