KN-92 phosphate

• CAT Number: I000510
• CAS Number: 1135280-28-2
• Molecular Formula: C24H28ClN2O7PS
• Molecular Weight: 554.98
• Purity: ≥95%
• Synonyms: (E)-N-(2-(((3-(4-chlorophenyl)allyl)(methyl)amino)methyl)phenyl)-4-methoxybenzenesulfonamide phosphate
• Target: P2X purinergic receptor
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IUPAC Name: N-[2-[[[(E)-3-(4-chlorophenyl)prop-2-enyl]-methylamino]methyl]phenyl]-4-methoxybenzenesulfonamide;phosphoric acid
• InChI: InChI=1S/C24H25ClN2O3S.H3O4P/c1-27(17-5-6-19-9-11-21(25)12-10-19)18-20-7-3-4-8-24(20)26-31(28,29)23-15-13-22(30-2)14-16-23;1-5(2,3)4/h3-16,26H,17-18H2,1-2H3;(H3,1,2,3,4)/b6-5+
• InChIKey: XRQHWVVDNMJDEQ-IPZCTEOASA-N
• SMILES: CN(C/C=C/C1=CC=C(C=C1)Cl)CC2=CC=CC=C2NS(=O)(=O)C3=CC=C(C=C3)OC.OP(=O)(O)O

KN-92 phosphate（Cat No.:I000510）is a selective inhibitor of calcium/calmodulin-dependent protein kinase II (CaMKII), a key enzyme involved in various cellular processes, including memory formation, synaptic plasticity, and muscle contraction. By inhibiting CaMKII, KN-92 phosphate can modulate signaling pathways related to neuronal function and cardiovascular health. It has been investigated for its potential in treating neurological conditions, such as Alzheimer’s disease and epilepsy, where CaMKII dysregulation is implicated. Additionally, KN-92 phosphate may have applications in studying the role of CaMKII in cellular signaling and its contribution to learning, memory, and muscle function.

Reference

[1]. Rokhlin OW, Guseva NV, Taghiyev AF et al. KN-93 inhibits androgen receptor activity and induces cell death irrespective of p53 and Akt status in prostate cancer. Cancer Biol Ther. 2010 Feb;9(3):224-35.
Abstract
It has been suggested that the downregulation of AR expression should be considered the principal strategy for the treatment of hormone-refractory prostate cancer. We have previously shown that inhibition of AR induced PI3K-independent activation of Akt that was mediated by CaMKII. In this study, we found that the CaMKII inhibitor KN-93 has a broader effect on apoptosis than just inhibition of CaMKII: first, KN-93 inhibits AR activity and induces cell death in PCa cells after androgen deprivation when many other drugs fail to kill prostate cancer cells; second, KN-93 inhibits expression of the anti-apoptotic protein Mcl-1 and induces expression of the pro-apoptotic protein PUMA; third, KN-93-mediated cell death is p53-independent; and fourth, KN-93 induces the generation of ROS. The ROS induction allows KN-93 to circumvent the activation of Akt, which occurs in prostate cancer cells under androgen deprivation, since Akt could not inhibit ROS-mediated apoptosis. KN-93 also synergistically induces cell death in combination with low doses of doxorubicin and converts the phenotype of prostate cancer cells from TRAIL-resistant to -sensitive. These data suggest that KN-93 could be used for novel therapeutic approaches when hormonal therapy has failed.
[2]. An P, Zhu JY, Yang Y et al. KN-93, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro. World J Gastroenterol. 2007 Mar 7;13(9):1445-8.
[3]. Gao L, Blair LA, Marshall J. et al. CaMKII-independent effects of KN93 and its inactive analog KN92: reversible inhibition of L-type calcium channels. Biochem Biophys Res Commun. 2006 Jul 14;345(4):1606-10.
[4]. Rezazadeh S, Claydon TW, Fedida D. et al. KN-93 (2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl)]amino-N-(4-chlorocinnamyl)-N-methylbenzylamine), a calcium/calmodulin-dependent protein kinase II inhibitor, is a direct extracellular blocker of voltage-gated potassium channels. J Pharmacol Exp Ther. 2006 Apr;317(1):292-9.
[5]. Anderson ME, Braun AP, Wu Y et al. KN-93, an inhibitor of multifunctional Ca++/calmodulin-dependent protein kinase, decreases early afterdepolarizations in rabbit heart. J Pharmacol Exp Ther. 1998 Dec;287(3):996-1006.
[6]. 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 PC12h cells. Biochem Biophys Res Commun. 1991 Dec 31;181(3):968-75.