KN-93 Phosphate

Cell lines

LX-2 cells

Preparation Method

LX-2 cells were incubated with 0, 5, 10, 25, 50μM of KN-93 Phosphate for 24h, and cell viability was then measured using the CCK-8 assay.

Reaction Conditions

0, 5, 10, 25, 50μM; 24h

Applications

After incubation of KN-93 Phosphate at various concentrations for 24h, the number of LX-2 cells reduced dramatically from 81.76% (5μM) to 27.15% (50μM).

Animal models

Sprague Dawley rats

Preparation Method

6-hydroxydopamine (OHDA) injections were used to create a rat model of Parkinson's disease (PD). After 3 weeks of injections, rats exhibiting stable apomorphine-induced rotations (≥0.7 turns/minute) were selected as valid PD rats. Forty of these PD rats were treated with levodopa plus benserazide twice daily for 21 days. Abnormal involuntary movement (AIM) scores were measured on days 1, 7, 14, and 21 of treatment. In addition, one group of PD rats (PD group, n=10) and another group of sham-operated rats (sham group, n=10) were treated with vehicle twice daily for 21 days. On day 22, the 40 levodopa-treated PD rats were randomly divided into four groups: levodopa+KN-93 Phosphate (1µg) group, levodopa+KN-93 Phosphate (2µg) group, levodoap+KN-93 Phosphate (5µg) group, and levodopa+vehicle group. These rats received intrastriatal injections of different doses of KN-93 Phosphate (1µg, 2µg, or 5µg) or vehicle before levodopa treatment. As a control, the sham group and PD group rats received intrastriatal injections of vehicle before vehicle treatment. Apomorphine-induced rotations were measured to assess the antiparkinsonian effect of KN-93 Phosphate on days 1 and 22. AIM scores were measured to assess the antidyskinetic effect of KN-93 Phosphate on days 1, 7, 14, 21, and 22. At the end of the experiment, rats were euthanized with deep anesthesia using 3% phenobarbital. Western blot analysis was used to determine the levels of GluR1 and pGluR1S845. Real-time polymerase chain reaction (PCR) was used to measure the levels of Gad1 and Nurr77.

Dosage form

1, 2, 5μg; 21 days; intrastriatally treated

Applications

2µg and 5µg KN-93 Phosphate treatment lowered AIMs scores in levodopa priming PD rats without affecting the antiparkinsonian effect of levodopa. In agreement with behavioral analysis, KN-93 Phosphate treatment reduced pGluR1S845 levels in PD rats. Moreover, KN-93 Phosphate treatment reduced the expression of Gad1 and Nur77 in PD rats.

References:
[1] An P, Zhu J Y, Yang Y, et al. KN-93 Phosphate, a specific inhibitor of CaMKII inhibits human hepatic stellate cell proliferation in vitro[J]. World Journal of Gastroenterology: WJG, 2007, 13(9): 1445.
[2]Yang X, Wu N, Song L, et al. Intrastriatal injections of KN-93 Phosphate ameliorates levodopa-induced dyskinesia in a rat model of Parkinson’s disease[J]. Neuropsychiatric disease and treatment, 2013: 1213-1220.