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KN-93 is a potent and selective inhibitor of CaM kinase II with IC50 value of 0.37μM.[1]

CaM kinase II means Ca2+/calmodulin-dependent protein kinase II which is a serine/threonine-specific protein kinase. It is regulated by the Ca2+/calmodulin complex. CaMKII has 28 different isoforms. The structure governs an autoinhibition which is the Threonine 286 residue. When this site is phosphorylated, it will permanently activate the CaMKII enzyme. The variable and self-associative domains of CaMKII enzyme govern the sensitivity to calcium and calmodulin. CaMKII is related to many signaling pathways. CaMKII is considered to play an important role in learning and memory. CaMKII is also important for reuptake in cardiomyocytes and Ca2+ homeostasis, and CD8 T-cell activation. Misregulation of CaMKII is considered to be related to Alzheimer’s disease, heart arrhythmia , and Angelman syndrome.[2]

KN-93 significantly inhibited CaM kinase activity at 0.5μM in vitro CaM kinase assay. KN-93 potent inhibited CaM kinase II activity In vitro CaM kinase activity with rabbit myocardium with Ki value of 2.58μM. [1] KN-93 inhibited cell growth at 12μM in NIH 3T3 cells and arrested cells in G1 cycle. KN-93 induced cell apoptosis at 24μM in NIH 3T3 cells. [3] KN-93 inhibits expression of Mcl-1which is an anti-apoptotic protein, It also induces p53-independent cell death in PCa cells. KN-93 also induces  the  generation  of ROS and inhibits AR activity then induces cell death.

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