Focused screening to identify new adenosine kinase inhibitors

Köse, Meryem; Schiedel, Anke C.; Bauer, Alexander Andreas; Poschenrieder, Hermann; Burbiel, Joachim C.; Akkinepally, Raghuram Rao; Stachef, Hans-Dietrich und Müller, Christa E. (2016): Focused screening to identify new adenosine kinase inhibitors. In: Bioorganic & Medicinal Chemistry, Bd. 24, Nr. 21: S. 5127-5133

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. (C) 2016 Elsevier Ltd. All rights reserved.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department für Pharmazie - Zentrum für Pharmaforschung
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 0968-0896
• Sprache: Englisch