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KN-93 is a water-soluble, selective inhibitor of Ca2+/calmodulin-dependent kinase II (CaMKII), competitively blocking CaM binding to the kinase (Ki = 370 nM).1 It does not affect the activities of PKA, PKC, MLCK, or Ca2+-phosphodiesterase.1 It inhibits histamine-induced aminopyrine uptake in parietal cells (IC50 = 300 nM).2 More recently, KN-93 has been used to implicate roles for CaMKII in Ca2+-induced Ca2+ release in cardiac myocytes, constitutive phosphorylation of 5-lipoxygenase in 3T3 cells, and Ca2+-dependent activation of HIF-1α in colon cancer cells.3,4,5
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1
Sumi, M., Kiuchi, K., Ishikawa, T., et al. The newly synthesized selective Ca2+/calmodulin dependent protein kinase II inhibitor KN-93 reduces dopamine contents in PC12th cells. Biochem Biophys Res Commun 181(3) 968-975 (1991).
2
Mamiya, N., Goldenring, J.R., Tsunoda, Y., et al. Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93. Biochem Biophys Res Commun 195(2) 608-615 (1993).
3
Oestreich, E.A., Malik, S., Goonasekera, S.A., et al. Epac and phospholipase Ce regulate Ca2+ release in the heart by activation of protein kinase Ce and calcium-calmodulin kinase II. J Biol Chem 284(3) 1514-1522 (2009).
4
Flamand, N., Luo, M., Peters-Golden, M., et al. Phosphorylation of serine 271 on 5-lipoxygenase and its role in nuclear export. J Biol Chem 284(1) 306-313 (2009).
5
Riganti, C., Doublier, S., Viarisio, D., et al. Artemisinin induces doxorubicin resistance in human colon cancer cells via calcium-dependent activation of HIF-1a and P-glycoprotein overexpression. Brit J Pharmacol 156 1054-1066 (2009).
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