1. Research Laboratories, Ikeda Mohando Co., Ltd., Kamiichi-machi, Toyama 930–03, Japan;2. Riken, The Institute of Physical and Chemical Research, Wako-shi, Saitama 351–01, Japan
Abstract:
KS-504a inhibited bovine brain calmodulin-dependent cyclic nucleotide phosphodieaterase (CaM-PDE) with an IC50 value of 122 μm. The inhibition was reversed by a high concentration of calmodulin. Cal modulin-independent activities of the enzyme were not affected by the compound at the same concentration ranges. Ca2+-dependent interaction of the compounds with calmodulin was shown using hydrophobic fluorescence probes. These data indicated that the compound exerted its effects on CaM-PDE by interacting with calmodulin. KS-504a also inhibited other calmodulin-dependent enzymes at different concentration ranges; myosin light chain kinase was inhibited at the lowest concentrations with an IC50 value of 6.3 μm. The inhibition mechanism was competetive with respect to calmodulin and non-competetive to ATP.