title: 'Turn On/Off' fluorescence probe for the screening of unactivated Bruton's tyrosine kinase.
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].
authors.affiliation: Drug Discovery Research, Carna Biosciences, Inc., 3rd Floor, BMA, 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: wataru.kawahata@carnabio.com.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kawahata
authors.affiliation: Drug Discovery Research, Carna Biosciences, Inc., 3rd Floor, BMA, 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Asami
authors.affiliation: Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Fujii
authors.affiliation: Drug Discovery Research, Carna Biosciences, Inc., 3rd Floor, BMA, 1-5-5 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Sawa
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D005456:Fluorescent Dyes / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000032:analysis* / Q000037:antagonists & inhibitors
chemical_list: D005456:Fluorescent Dyes; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase
keywords: Binding assay; Bruton’s tyrosine kinase; Fluorescence probe; Kinase inhibitor