| Name | Ranolazine |
| Description | 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. |
| Kinase Assay | 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. |
| In vitro | In the absence and presence of IK-blocking drugs, when late INa is increased, Ranolazine inhibits the late component of INa and attenuates prolongation of action potential duration. Ranolazine (10 mM) reduces by 89% of the 13.6-fold increase in variability of APD caused by 10 nM ATX-II. Ranolazine is found to bind more tightly to the inactivated state than the resting state of the sodium channel underlying I(NaL), with apparent dissociation constants K(dr)=7.47 mM and K(di)=1.71 mM, respectively. Ranolazine（5 mM and 10 mM） reversibly shortens the duration of TCs and abolishes the after contraction. |
| In vivo | In dog left ventricular myocytes, Ranolazine significantly and reversibly stimulate the action potential duration (APD) of shortened myocytes at 0.5 or 0.25 Hz in a concentration-dependent manner. In rat hearts, Ranolazine (10 mM) significantly increased 1.5-fold to 3-fold under glucose oxidation conditions. Ranolazine (10 mM) also increased glucose oxidation (high calcium, low FA; 15 ml/min) in Langendorff hearts in normoxic rats. Ranolazine significantly improves the function of the reperfused ischemic working heart, which is associated with a significant increase in glucose oxidation function. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2 mg/mL (4.68 mM), Sonication is recommended.
Ethanol : 16 mg/mL (37.42 mM), Sonication is recommended.
DMSO : 100 mg/mL (233.9 mM), Sonication is recommended.
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| Keywords | SodiumChannel | Sodium Channel | Ranolazine | Na+ channels | Na channels | Inhibitor | inhibit | CVT-303 | CVT303 | CalciumChannel | Calcium Channel | Ca2+ channels | Ca channels |
| Inhibitors Related | Quadrol | 2,4,6-Tri-tert-butylphenol | Phenytoin sodium | Chlorocresol | Procaine | L-Ascorbic acid | Valproic Acid | L-Aspartic aicd sodium | L-Ascorbic acid sodium salt | 2-Nitrobenzoic acid | Magnesium Chloride Hexahydrate | Magnesium sulfate |
| Related Compound Libraries | Failed Clinical Trials Compound Library | Bioactive Compound Library | Pain-Related Compound Library | Membrane Protein-targeted Compound Library | EMA Approved Drug Library | Drug Repurposing Compound Library | Neuroprotective Compound Library | Inhibitor Library | Anti-Cancer Approved Drug Library | FDA-Approved Drug Library | Bioactive Compounds Library Max | Ion Channel Targeted Library |
United States
