KN-93 (Phosphate) can competitively block the binding of calmodulin to the corresponding kinase. It is a calcium/calmodulin-dependent kinase II (CaMKII) inhibitor with a Ki of 370 nM. It can also inhibit the proliferation of human hepatic stellate cells.

CaMK II:0.37 μM(Ki)

METHODS: PCI2h cells were treated with KN-93 (0, 1, 2, 5, 10 μM) and dopamine content was measured.
RESULTS KN-93 reduced dopamine (DA) content in a dose-dependent manner. [3]
METHODS: Human hepatic stellate cells (LX-2) were treated with KN-93 (0-50 μM), cell proliferation was detected by CCK-8 method, and the expression of two cell cycle regulators, p53 and p21, was detected by SDS-PAGE and Western blotting.
RESULTS KN-93 (5-50 μM) reduced the proliferation of human hepatic stellate cells in a dose-dependent manner, from 81.76% to 27.15% after 24 hours of treatment; 10 μM KN-93 incubation induced a time-dependent decrease in cell growth, from 78.27% at 8 h to 11.48% at 48 h; cell cycle regulator expression analysis showed that KN-93 reduced the expression of p53 and p21. [5]

METHODS: 6-hydroxydopamine (OHDA) injection induced PD model in rats, and different doses of KN-93 (1 μg, 2 μg, or 5 μg) were administered into the striatum of successfully lesioned rats before L-DOPA treatment. Abnormal involuntary movement (AIM) scores and apomorphine-induced rotations were measured in PD rats. Phosphorylation level of GluR1 at Serine-845 (pGluR1S845) level was determined by western blot. Arc and Penk levels were measured by real-time polymerase chain reaction (PCR).
RESULTS Both 2 μg and 5 μg KN-93 treatment reduced the AIMs scores of L-dopa-induced PD rats without affecting the anti-parkinsonian effect of L-dopa; consistent with behavioral analysis, KN-93 (2 μg) treatment reduced the level of pGluR1S845 in PD rats and also reduced the expression of Gad1 and Nur77 in PD rats. [1]
METHODS: KN-93 (0.24 mg/kg, intraperitoneal injection, three times a week) treated MRL/lpr Foxp3-GFP mice, harvested lymphoid organs, and determined the number of Foxp3 cells; from MRL/lpr Foxp3-GFP mice Naïve CD4 cells were isolated from the spleen and cultured in vitro under Treg polarizing conditions to determine whether they could prevent disease progression.
RESULTS Treg cells in PBS-treated mice gradually decreased, while Treg cells in KN-93-treated mice remained stable and significantly increased; more GFP-positive cells were found in the spleen and peripheral lymph nodes of KN-93-treated mice. ; The percentage of Treg cells was higher in the presence of KN-93 in a dose-dependent manner. [2]