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Purity: ≥98%
| Targets |
Cariporide targets the sodium-hydrogen exchanger subtype 1 (NHE-1), a transmembrane protein that regulates intracellular pH by exchanging extracellular sodium ions for intracellular protons. NHE-1 is ubiquitously expressed and plays a critical role in maintaining intracellular pH homeostasis, particularly in cardiac myocytes during ischemia-reperfusion injury. By inhibiting NHE-1, cariporide prevents the accumulation of intracellular sodium that occurs during ischemia, which in turn reduces calcium overload and prevents cardiomyocyte apoptosis. The compound exhibits potent inhibition of NHE1 (IC50 = 30 nM) with selectivity over NHE2 and NHE3.
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| ln Vitro |
At 8 or 16 hours, ciprofloxacin dramatically reduced cell death indicators such TUNEL positivity and caspase-3 cleavage. The buildup of Na+ and Ca2+ in the cytoplasm is strongly inhibited by carboride. Cariporide inhibits H2+O2+-induced decrease of mitochondrial membrane potential [1]. By blocking Na+/H+ exchange, ciporide (HOE-642) lowers cytosolic Ca2+ in cardiomyocytes, reducing cardiac ischemia/reperfusion injury [2]. Human platelet degranulation, platelet leukocyte aggregation formation, and GPIIb/IIIa receptor (PAC-1) activation are all inhibited by carbariporide (HOE-642) [3].
In vitro, cariporide acts as a potent and selective inhibitor of NHE-1. It inhibits NHE1-mediated sodium-hydrogen exchange in CHO-K1 cells expressing human NHE1 with an IC50 of 30 nM. The compound shows selectivity for NHE1 over NHE2 and NHE3, with IC50 values of 0.05, 3, and 1000 μM for NHE1, NHE3, and NHE2, respectively. These studies confirm the compound's mechanism of action as a selective NHE1 inhibitor. Cariporide has been shown to prevent cardiomyocyte apoptosis in vitro. |
| ln Vivo |
Caripoli injection intravenously dramatically lowers cerebral edema, brain swelling, and infarct volume in addition to brain Na+ uptake [4].
In vivo, cariporide has been studied for its cardioprotective effects in animal models of ischemia-reperfusion injury. By inhibiting NHE1, the compound reduces intracellular sodium and calcium overload during ischemia, thereby protecting cardiac myocytes from ischemic damage. Cariporide has been shown to reduce infarct size and improve cardiac function in animal models of myocardial infarction. The compound's efficacy in preventing ischemic injury supports its potential as a therapeutic agent for cardiovascular diseases. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assays for cariporide are not applicable because NHE-1 is a transporter protein rather than a classical enzyme or receptor. However, the compound's activity can be assessed using cell-based assays that measure sodium-hydrogen exchange activity. In these assays, cells expressing NHE1 are loaded with a pH-sensitive fluorescent dye, and the rate of intracellular pH recovery following an acid load is measured in the presence of varying concentrations of cariporide. The IC50 for inhibition of NHE1 activity is determined from the dose-response curve.
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| Cell Assay |
In vitro cellular assays for cariporide are performed using cell lines expressing NHE1, such as CHO-K1 cells transfected with human NHE1. Cells are loaded with a pH-sensitive dye (e.g., BCECF), and intracellular pH is monitored spectrofluorometrically. An acid load is induced by ammonium chloride prepulse, and the rate of pH recovery is measured in the presence of varying concentrations of cariporide. The IC50 for inhibition of NHE1-mediated pH recovery is determined. Additionally, the compound's ability to prevent cardiomyocyte apoptosis can be assessed using cardiac cell lines exposed to ischemic conditions.
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| Animal Protocol |
In vivo animal experiments for cariporide are conducted in rodent models of myocardial ischemia-reperfusion injury. Rats or mice are subjected to temporary coronary artery occlusion followed by reperfusion, and cariporide is administered prior to ischemia or at the time of reperfusion. The primary endpoints include infarct size, cardiac function (measured by echocardiography), and serum markers of cardiac injury. The compound's ability to reduce infarct size and improve functional recovery is evaluated. Other models of ischemic injury, such as stroke or renal ischemia, may also be used.
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| ADME/Pharmacokinetics |
Cariporide has a molecular weight of 283.35 g/mol and a molecular formula of C12H17N3O3S. The compound is orally active. Detailed pharmacokinetic parameters such as half-life, Cmax, and bioavailability are not extensively reported in the available literature. However, the compound's in vivo efficacy in animal models suggests adequate systemic exposure following oral or parenteral administration. Cariporide is soluble in DMSO and other organic solvents.
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| Toxicity/Toxicokinetics |
Cariporide has been evaluated in preclinical studies and has been reported to be well-tolerated at effective doses. No significant toxicity has been reported in the available literature. However, comprehensive toxicology studies would be necessary to fully assess the compound's safety profile for clinical development. As a selective NHE1 inhibitor, cariporide may have a favorable safety profile, but potential effects on other NHE isoforms or off-target effects would need to be evaluated.
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| References |
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| Additional Infomation |
See also: Calipole mesylate (note moved to).
Drug Indications Studied for use in cardiac surgery. Mechanism of Action Calipolide is a selective sodium-hydrogen reverse transporter inhibitor. Sodium-hydrogen exchangers play a crucial role in the pathophysiology of myocardial ischemia-reperfusion injury. During ischemia, the accumulation of hydrogen ions in the cytoplasm of cardiomyocytes creates a proton gradient, promoting hydrogen ion efflux and sodium ion influx. This sodium ion accumulation can secondaryly activate the sodium-calcium exchanger, causing it to reverse its function, leading to a net accumulation of calcium ions in the cytoplasm of cardiomyocytes, which in turn leads to dysfunction and cell death. Calipole, by inhibiting sodium-hydrogen exchange, prevents the accumulation of calcium ions in the cytoplasm, thereby reducing the infarct area. Cariporide is a selective and potent inhibitor of the sodium-hydrogen exchanger subtype 1 (NHE-1). It has an IC50 of 30 nM for human NHE1 and shows selectivity over NHE2 and NHE3. Cariporide is used primarily for research purposes in cardiovascular studies to protect cells from ischemic damage. The compound prevents cardiomyocyte apoptosis and has shown efficacy in reducing infarct size in animal models of myocardial ischemia-reperfusion injury. Cariporide is not an approved drug but is a valuable tool for studying the role of NHE1 in cardiovascular diseases. |
| Molecular Formula |
C12H17N3O3S
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| Molecular Weight |
283.34
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| Exact Mass |
283.099
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| CAS # |
159138-80-4
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| Related CAS # |
Cariporide (mesilate);159138-81-5
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| PubChem CID |
151172
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
542.8±60.0 °C at 760 mmHg
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| Flash Point |
282.1±32.9 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.602
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| LogP |
0.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
461
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
IWXNYAIICFKCTM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H17N3O3S/c1-7(2)9-5-4-8(11(16)15-12(13)14)6-10(9)19(3,17)18/h4-7H,1-3H3,(H4,13,14,15,16)
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| Chemical Name |
N-(Diaminomethylidene)-3-methylsulfonyl-4-propan-2-ylbenzamide
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| Synonyms |
Cariporide HOE642 HOE-642 HOE 642
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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 : ≥ 100 mg/mL (~352.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.82 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 25.0 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: ≥ 2.5 mg/mL (8.82 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 25.0 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: ≥ 2.5 mg/mL (8.82 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 | 3.5293 mL | 17.6466 mL | 35.2933 mL | |
| 5 mM | 0.7059 mL | 3.5293 mL | 7.0587 mL | |
| 10 mM | 0.3529 mL | 1.7647 mL | 3.5293 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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