Focused screening to identify new adenosine kinase inhibitors.

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 Ki value of 184nM. 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.