'Turn On/Off' fluorescence probe for the screening of unactivated Bruton's tyrosine kinase. Issue 10 (15th May 2015)

• Record Type: Journal Article
• Authors: Kawahata, Wataru; Asami, Tokiko; Fujii, Ikuo; Sawa, Masaaki
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 25:Issue 10(2015)
• Page Start: 2141
• Page End: 2145
• Publication Date: 2015-05-15
• Subjects: Bruton's tyrosine kinase -- Fluorescence probe -- Kinase inhibitor -- Binding assay; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.03.063
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: BTK has emerged as a promising target for treating B-cell malignancies and autoimmune diseases, and there has been a growing demand to identify selective BTK inhibitors efficiently. In this Letter, we have designed and synthesized a new fluorescent probe to screen compounds that preferentially bind to an unactivated state of BTK (BTK [U]). The fluorescence of the probe was turned on in the presence of BTK [U], and quenched by the addition of compounds which preferentially bind to BTK [U]. This unique fluorescent probe was successfully applied to the screening of a kinase focused compound library. The results suggest that this new method is a simple and easy-to-perform assay to screen inhibitors of BTK [U].