KCS

Adenosine kinase (AK) is a ubiquitous intracellular enzyme, which catalyzes the phosphorylation of adenosine (ADO) to adenosine monophosphate (AMP), and therefore is a key enzyme in the control of cellular concentrations of ADO and thus AK inhibitors have therapeutic potential as analgesic and anti-inflammatory agents. A chemical feature based pharmacophore model has been generated for AK from known inhibitors by HypoGen module implemented in CATALYST software. The top ranked hypothesis (Hypo1) contains four features: two hydrogen-bond acceptors (HA), two hydrophobic aromatics (Z). Hypo1 was validated by 124 test set molecules as well as CatScramble validation method and was used for searching new compounds from NCI chemical database. These new compounds were screened on the basis of limiting by activity and Lipinski’s rule. Finally, 200 compounds were selected for molecular docking and were docked into both the ADO binding site and the ATP binding site of AK. Docking results revealed that the ratio of compounds that bound to ADO/ATP site were in proportion to that of the most active compounds ratio of the training set.