Ranolazine (RS 43285-003) is a calcium uptake inhibitor via the sodium/calcium channel, used to treat chronic angina. It affects the sodium-dependent calcium channels during myocardial ischemia in rabbits by altering the intracellular sodium level.

INa:6 μM (IC50), IKr:12 μM (IC50)

在IK阻断化合物的存在与否下，当晚期INa增加时，Ranolazine抑制INa的晚期成分并减少动作电位持续时间的延长。Ranolazine（10 mM）降低了由10 nM ATX-II引起的APD变异性13.6倍增加的89%。研究发现，与INaL底下的钠通道的休息态相比，Ranolazine与失活态结合更紧，其表观解离常数K(dr)=7.47 mM和K(di)=1.71 mM。Ranolazine（5 mM和10 mM）可逆地缩短TCs的持续时间并消除后收缩。

在犬左心室心肌细胞中，Ranolazine 显著且可逆地以浓度依赖的方式刺激缩短的心肌细胞的动作电位时程（APD），在0.5或0.25 Hz时效果显著。在大鼠心脏中，Ranolazine（10 mM）在葡萄糖氧化条件下显著增加1.5倍至3倍。同时，Ranolazine（10 mM）也提高了Langendorff心脏模型中正常氧合大鼠心脏的葡萄糖氧化（高钙，低FA；15 ml/min）。Ranolazine显著改善了再灌注缺血工作心脏的功能，这与葡萄糖氧化功能的显著增加有关。

In vitro kinase assay for CDK1 and Aurora kinases:CDK1 kinase activity is tested by the CDK1/cyclin B complex purified from baculovirus to phosphorylate a biotinylated peptide substrate containing the consensus phosphorylation site for histone H1, which is phosphorylated in vivo by CDK1. Inhibition of CDK1 activity is measured by observing a decreased amount of 33P-γ-ATP incorporation into the immobilized substrate in streptavidin-coated 96-well scintillating microplates. CDK1 enzyme is diluted in 50 mM Tris-HCl (pH 8), 10 mM MgCl2, 0.1 mM Na3VO4, 1 mM DTT, 1% DMSO, 0.25 μM peptide, 0.1 μCi per well 33P-γ-ATP, and 5 μM ATP in the presence or absence of various concentrations of JNJ-7706621 and incubated at 30 °C for 1 hour. The reaction is terminated by washing with PBS containing 100 mM EDTA and plates are counted in a scintillation counter. IC50 is determined by Linear regression analysis of the percent inhibition by JNJ-7706621.The Aurora kinase activity is measured with 10 μM ATP and a peptide containing a dual repeat of the kemptide phosphorylation motif.