Focused screening to identify new adenosine kinase inhibitors. Issue 21 (1st November 2016)

• Record Type: Journal Article
• Authors: Köse, Meryem; Schiedel, Anke C.; Bauer, Alexander Andreas; Poschenrieder, Hermann; Burbiel, Joachim C.; Akkinepally, Raghuram Rao; Stachel, Hans-Dietrich; Müller, Christa E.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 21(2016)
• Page Start: 5127
• Page End: 5133
• Publication Date: 2016-11-01
• Subjects: Adenosine kinase assay -- High-throughput screening -- Adenosine kinase inhibitors -- Compound library -- Adenosine homeostasis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.08.026
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Adenosine kinase (AdK) is a key player in controlling intra- and extracellular concentrations of the signaling molecule adenosine. Extensive evidence points to an important role of AdK in several diseases, and suggests that AdK inhibition might be a promising therapeutic strategy. The development of a new AdK assay and subsequent screening of part of our focused compound library led to the identification of 12 hit compounds (hit rate of 6%) representing six new classes of non-nucleoside human AdK inhibitors. The most potent inhibitor 1 displayed a K i value of 184 nM. Compound screening with a newly developed assay was useful and efficient for discovering novel AdK inhibitors which may serve as lead structures for developing drugs for adenosine augmentation therapy.