Adenosine Kinase Inhibitors

Adenosine kinase (ADK) is a highly conserved monomeric enzyme that constitutes the primary route of adenosine metabolism under normal conditions. ADK acts to decrease intracellular adenosine levels by catalyzing its conversion into AMP and ADP, using ATP as a phosphate donor and a divalent cation, for example Mg²⁺, as a co-factor.

ADK is regulated by inorganic phosphate levels, the concentration of local free Mg²⁺ and contains a NXXE motif that is vital for phosphate activation. Inhibition of this enzyme has been implicated in tissue-protective mechanisms against various physiological stresses, including ischemia, seizures, pain and inflammation, thus there is much interest in developing pharmacological ADK inhibitors.