Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C.

  title={Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C.},
  author={Hiroyoshi Hidaka and Masaki Inagaki and Sachiyo Kawamoto and Yasuharu Sasaki},
  volume={23 21},
Naphthalenesulfonamides such as N-(6-amino-hexyl)-5-chloro-1-naphthalenesulfonamide (W-7) are potent calmodulin (CaM) antagonists and act upon several protein kinases at higher concentration. When the naphthalene ring was replaced by isoquinoline, the derivatives were no longer CaM antagonists but retained the ability to inhibit protein kinases, and some of the derivatives exhibited selective inhibition toward a certain protein kinase. cAMP-dependent, cGMP-dependent, and Ca2+-phospholipid… 
Selective inhibition of cyclic AMP-dependent protein kinase by isoquinoline derivatives.
The very potent isoquinoline-derived cAK inhibitors found here involve substitution of the N-containingisoquinoline ring system and these inhibitors show high specificity for cAK.
HMN-709, a chlorobenzenesulfonamide derivative, is a new membrane-permeable calmodulin antagonist.
The results suggest that HMN-709 antagonizes calmodulin by binding to Ca2+/calmodulin, and appears to be a new, membrane-permeableCalmodulin antagonist that may be used for studying the involvement of cal modulin in cellular processes.
Specific inhibition of cyclic AMP-dependent protein kinase by the antimalarial halofantrine and by related phenanthrenes.
The selective, high affinity interaction of halofantrine with cAK may contribute to biological effects in vivo of this clinically-employed antimalarial compound.
Development of specific Rho-kinase inhibitors and their clinical application.


Two types of calcium-dependent protein phosphorylations modulated by calmodulin antagonists. Naphthalenesulfonamide derivatives.
Ca2-dependent protein phosphorylations activated by calmodulin or phospholipid were studied using selective inhibitors. Both protein phosphorylations were inhibited by
Calcium-regulated modulator protein interacting agents inhibit smooth muscle calcium-stimulated protein kinase and ATPase.
The results suggest that agents that interact with modulator protein produce relaxation of smooth muscle by inhibition of modulatorprotein-dependent myosin light chain phosphorylation thus suppressing the actin-myosin interaction and concomitant myOSin ATPase activation.
Effects of the calmodulin antagonist, fluphenazine, on phosphorylation of myosin and phosphorylase in intact smooth muscle.
The effects of the phenothiazine, fluphenazine, on isometric tension development and phosphorylation of phosphorylase and the phosphorylatable light chain of myosin in intact bovine tracheal smooth muscle were examined and inhibition of contractile activity in intact smooth muscle by anticalmodulin agents may be directly related to inhibition of P-light chain phosphorylated.
Calcium, phospholipid turnover and transmembrane signalling.
  • Y. Nishizuka
  • Biology, Computer Science
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1983
It is shown that either receptor-linked protein phosphorylation or Ca2+ mobilization alone is merely a prerequisite but not a sufficient requirement, and both are synergistically effective for causing a full physiological cellular response.