生物活性

• 靶点	CaMKII Ki:0.37μM

• 描述KN-93 Phosphate is the phosphate form of KN-93. KN-93 is a CaMKII (Calcium/calmodulin-dependent protein kinase II) blocker. It elicited potent inhibitory effects on CaMKII phosphorylating activity with an inhibition constant of 0.37μM but had no significant effects on the catalytic activity of CAMP-dependent protein kinase, Ca²⁺/phospholipid dependent protein kinase, myosin light chain kinase and Ca²⁺-phosphodiesterase. KN-93 also inhibited the autophosphorylation of both the α- and β-subunits of CaMKII. KN-93 inhibited dopamine formation by modulating the reaction rate of TH to reduce the Ca²⁺-mediated phosphorylation levels of the tyrosine hydroxylase molecule in PC12h cells. KN-93 also works as a direct extracellular blocker of voltage-gated potassium channels with IC50 value of 307±12nM for block of the Kv1.5. KN-93 acted through promotion and stabilization of C-type inactivation. KN-93 was ineffective as a blocker when applied intracellularly, suggesting that CaMK II-independent effects of KN-93 on Kv channels can be circumvented by intracellular application of KN-93. KN-93 inhibits I_Kr in mammalian cardiomyocytes.

• 动物研究
  剂量	Rat: 0.501 μg/kg[3] (p.o.), 1 mg/kg[4] (i.p.) Woodchucks: 125 μg/kg[5] (osmotic minipumps) Mice: 4 mg/kg (i.p.)
  给药途径	p.o., osmotic minipumps, i.p.