Abstract:
:Bruton's Tyrosine Kinase (BTK) is one of the crucial kinases for the B cell maturation and mast cell activation, and specific inhibitors of BTK are considered to be attractive targets in drug discovery research. In this Letter, we have designed and synthesized a new fluorescent probe for TR-FRET-based high-throughput screening, to identify compounds that preferentially bind to an inactive conformation of BTK which has a unique structural feature. A set of kinase-focused compound library was screened using this assay method, and compound 31 was successfully identified as a potent inhibitor which preferentially bind to the inactive conformation of BTK. These results suggest that this screening method has a great potential for the discovery of novel selective BTK inhibitors.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Asami T,Kawahata W,Sawa Mdoi
10.1016/j.bmcl.2015.04.001subject
Has Abstractpub_date
2015-01-01 00:00:00pages
2033-6issue
10eissn
0960-894Xissn
1464-3405pii
S0960-894X(15)00303-0journal_volume
25pub_type
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