KN-62 is a cell-permeable, reversible, and selective inhibitor of CaM kinase II (Ki = 900 nM for rat brain CaM kinase II). KN-62 is also a potent non-competitive antagonist at the P2X7 receptor (IC50 = 15 nM). KN-62 inhibits the growth of K562 cells in a dose-dependent manner. KN-62 could inhibit the Ca2+/CaM kinase II activity in vivo. However, KN-62 only slightly influenced PC secretion from type II cells stimulated by phorbol 12-myristate 13-acetate, terbutaline and ATP that are known to increase surfactant secretion via the protein kinase C and protein kinase A pathways. KN-62 affects the interaction between calmodulin and Ca2+/CaM kinase II following inhibition of this kinase activity by directly binding to the calmodulin binding site of the enzyme but does not affect the calmodulin-independent activity of already autophosphorylated (activated) enzyme.