| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
Sodium-calcium exchanger (NCX).
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| ln Vitro |
In dog ventricular myocytes, concentration-dependent reduction of NCX currents is observed with ORM-10962 (10 nM, 100 nM, and 1 μM), with estimated IC50 values of 55 and 67 nM mV at -80 and 20 mV, respectively [1].
In vitro, ORM-10962 decreases NCX current in dog ventricular myocytes in a concentration-dependent manner. The estimated IC₅0 values for NCX current inhibition are 55 nM at -80 mV and 67 nM at 20 mV. The compound shows high selectivity for NCX over other ion channels and transporters, making it a valuable tool for studying the physiological and pathophysiological roles of NCX in cardiac tissue. |
| ln Vivo |
In anesthetized guinea pigs, the administration of ORM-10962 (0.3 mg/kg, IV, once) markedly postpones the onset of anesthesia and premature ventricular contractions (about 50%) or ventricular tachycardia (about 30%) [1].
In vivo, ORM-10962 (0.3 mg/kg, intravenous, single dose) pre-treatment significantly delays the development and recurrence of ventricular extrasystoles (by approximately 50%) and ventricular tachycardia (by approximately 30%) in anesthetized guinea pigs. These findings demonstrate the antiarrhythmic potential of NCX inhibition and support the role of NCX in cardiac arrhythmia generation. |
| Enzyme Assay |
NCX inhibition is assessed using patch-clamp electrophysiology in isolated cardiac myocytes. Dog ventricular myocytes are isolated by enzymatic digestion and maintained in Tyrode's solution. Whole-cell patch-clamp recordings are performed at room temperature. NCX current (INCX) is elicited by voltage ramp protocols in the presence of appropriate ion gradients and inhibitors of other currents (e.g., L-type Ca2+ channels, Na+/K+-ATPase). ORM-10962 is applied extracellularly at concentrations ranging from 1 nM to 10 microM. Current inhibition is calculated as the percentage reduction in INCX relative to control. IC₅0 values are determined by fitting dose-response data to the Hill equation. For receptor binding studies, radioligand binding assays using [3H]-ORM-10962 or related NCX inhibitors can be employed, though such assays are not standard for this compound.
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| Cell Assay |
Cellular assays for NCX activity are performed using cell lines or primary myocytes loaded with fluorescent calcium indicators (e.g., Fura-2 AM). Cells are subjected to protocols that drive NCX activity (e.g., Na+-loaded conditions followed by Ca2+-free reintroduction). ORM-10962 is added at concentrations of 10 nM, 100 nM, and 1 microM. The rate of Ca2+ extrusion or entry via NCX is measured by monitoring fluorescence changes. The extent of NCX inhibition is calculated by comparing Ca2+ flux rates in the presence and absence of the inhibitor. Alternatively, ion flux assays using radioactive tracers (⁴⁵Ca2+ or 22Na+) can be employed.
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| Animal Protocol |
Animal/Disease Models: Male guinea pigs (250-300 g) [1]
Doses: 0.3 mg/kg Route of Administration: intravenous (iv) (iv)injection, 10 minutes before starting ouabain infusion Experimental Results: Significant delay in the development of premature ventricular contractions (from 24 in the control group ±1.7 minutes to 36.6±2.7 minutes in the presence of drug) or ventricular tachycardia (from 31.8±1.8 minutes in the control group to 40.8±2.1 minutes in the presence of drug). In vivo efficacy is evaluated in anesthetized guinea pig models. Guinea pigs are anesthetized and instrumented for electrocardiogram (ECG) recording. ORM-10962 is administered intravenously at a dose of 0.3 mg/kg as a single bolus or pre-treatment. Cardiac arrhythmias are induced by programmed electrical stimulation or by administration of arrhythmogenic agents. The primary endpoints are the incidence and duration of ventricular extrasystoles and ventricular tachycardia. The compound's ability to delay arrhythmia development and reduce arrhythmia recurrence is quantified. For pharmacokinetic studies, blood samples are collected at multiple time points post-administration for determination of plasma drug concentrations. |
| ADME/Pharmacokinetics |
ORM-10962 has molecular formula C2₇H2₉N3O4 and molecular weight 459.54. The compound is typically administered intravenously in vivo due to its small-molecule properties. Pharmacokinetic parameters such as half-life, volume of distribution, and clearance have not been extensively reported in publicly available literature. The compound is stored as a powder at -20degC (stable for 3 years) or in solvent at -80degC (6 months). It is soluble in appropriate organic solvents for formulation.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for ORM-10962 in the available literature. As a selective NCX inhibitor, the compound is expected to have a favorable safety profile at pharmacological doses, though cardiac effects (both therapeutic and potential proarrhythmic) should be carefully monitored. The compound is for research use only and not for human therapeutic use. Standard laboratory safety precautions should be observed when handling. Acute toxicity and long-term safety data are not available.
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| References |
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| Additional Infomation |
Orm-10962 is an organic molecular entity that is an ion transport inhibitor and a selective inhibitor of the Na+-Ca2+ exchanger (NCX) in cardiomyocytes.
ORM-10962 is a research tool compound developed for studying the role of NCX in cardiac electrophysiology. It is one of the most selective NCX inhibitors available, with IC₅0 values in the nanomolar range for both forward and reverse modes of NCX activity. The compound has been used in multiple published studies investigating NCX function in ventricular myocytes, sinus node pacemaking, and cardiac arrhythmias. ORM-10962 is not an approved drug and is intended for research purposes only. It is available as a solid with purity specifications for research use. |
| Molecular Formula |
C27H29N3O4
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|---|---|
| Molecular Weight |
459.5369
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| Exact Mass |
459.215
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| CAS # |
763926-98-3
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| PubChem CID |
69016811
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.7
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
34
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| Complexity |
650
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C1([H])C([H])([H])C([H])([H])N(C([H])([H])C(N([H])C2=C([H])N=C(C([H])=C2[H])OC2C([H])=C([H])C3=C(C=2[H])C([H])([H])C([H])([H])C([H])(C2C([H])=C([H])C([H])=C([H])C=2[H])O3)=O)C([H])([H])C1([H])[H]
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| InChi Key |
UPGUBLDTYLMRHO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C27H29N3O4/c31-22-12-14-30(15-13-22)18-26(32)29-21-7-11-27(28-17-21)33-23-8-10-25-20(16-23)6-9-24(34-25)19-4-2-1-3-5-19/h1-5,7-8,10-11,16-17,22,24,31H,6,9,12-15,18H2,(H,29,32)
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| Chemical Name |
2-(4-hydroxypiperidin-1-yl)-N-[6-[(2-phenyl-3,4-dihydro-2H-chromen-6-yl)oxy]pyridin-3-yl]acetamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~544.02 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1761 mL | 10.8804 mL | 21.7609 mL | |
| 5 mM | 0.4352 mL | 2.1761 mL | 4.3522 mL | |
| 10 mM | 0.2176 mL | 1.0880 mL | 2.1761 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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