| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Antiporter[1]
Dimethylamiloride targets the Na⁺/H⁺ exchanger (NHE) family of antiporters, which are integral membrane proteins that exchange intracellular H⁺ for extracellular Na⁺. NHE1 is ubiquitously expressed and plays a critical role in intracellular pH regulation, cell volume control, and cell proliferation. NHE2 and NHE3 are primarily expressed in the gastrointestinal tract and kidney, where they are involved in sodium absorption and acid-base balance. Dimethylamiloride inhibits NHE1 with high potency (Ki = 0.02 μM), NHE2 with moderate potency (Ki = 0.25 μM), and NHE3 with low potency (Ki = 14 μM). |
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| ln Vitro |
In vitro, Dimethylamiloride inhibits Na⁺/H⁺ exchange activity in various cell types. The compound reduces intracellular pH recovery after acid loading and inhibits cell proliferation. In cancer cells, Dimethylamiloride inhibits cell proliferation and induces apoptosis. It modulates the activity of ion channels and transporters involved in the regulation of intracellular pH and calcium levels. The compound has been used to study the role of NHE in cell migration, invasion, and metastasis. Its effects are concentration-dependent and correlate with its NHE inhibitory potency.
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| ln Vivo |
In vivo, Dimethylamiloride has been studied for its effects on cardiac function and ischemic injury. The compound has been used to reduce cardiac dysfunction following ischemic injury in perfused rat ventricle models. Studies with ouabain indicated that this effect was due to blockade of sarcolemmal Na⁺ uptake into cardiac muscle. Dimethylamiloride has also been studied in models of cancer, where NHE inhibition may suppress tumor growth. However, its in vivo applications are primarily in research settings rather than therapeutic use.
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| Enzyme Assay |
Non-cell-based assays for Dimethylamiloride involve measuring Na⁺/H⁺ exchanger activity in membrane preparations or reconstituted systems. NHE activity is measured by monitoring pH-dependent Na⁺ uptake or H⁺ efflux using fluorescent pH indicators (e.g., BCECF) or radiolabeled tracers (²²Na⁺). Membrane vesicles or liposomes containing NHE are incubated with Dimethylamiloride at various concentrations, and transport activity is measured. IC₅₀ values are calculated from dose-response curves. Binding affinity to NHE can be measured using radioligand binding assays.
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| Cell Assay |
Cellular assays for Dimethylamiloride are performed using various cell lines expressing different NHE isoforms. Cells are treated with Dimethylamiloride at various concentrations, and NHE activity is measured by monitoring intracellular pH recovery after acid loading using fluorescent pH indicators (BCECF). Cell proliferation is measured by MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V/PI staining. Cell migration and invasion are evaluated using Transwell or scratch wound assays. Intracellular pH, sodium levels, and calcium levels are measured using fluorescent dyes.
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| Animal Protocol |
In vivo experiments with Dimethylamiloride are conducted in animal models of cardiac ischemia, cancer, or other conditions where NHE plays a role. In cardiac ischemia models, animals are subjected to ischemia-reperfusion injury, and Dimethylamiloride is administered before or after ischemia. Cardiac function is assessed by echocardiography or pressure-volume measurements. Infarct size is measured by histology. In cancer models, tumor growth inhibition is evaluated. Pharmacodynamic markers including NHE activity, intracellular pH, and downstream signaling are measured.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of Dimethylamiloride have been characterized in preclinical studies. As a small molecule amiloride analog, Dimethylamiloride is orally bioavailable and distributes to tissues. The compound has a molecular weight of 257.68 and is formulated as a hydrochloride salt. PK parameters including absorption, half-life, clearance, and volume of distribution have been studied. The compound is metabolized in the liver and excreted via urine. Its ability to cross the blood-brain barrier is limited. However, detailed PK data are less extensive than for other NHE inhibitors.
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| Toxicity/Toxicokinetics |
The toxicity of Dimethylamiloride has been evaluated in preclinical studies. As an NHE inhibitor, potential toxicities relate to disruption of intracellular pH regulation and sodium homeostasis. At high doses, the compound may cause electrolyte imbalances, cardiac arrhythmias, and renal dysfunction. In animal studies, Dimethylamiloride is tolerated at therapeutic doses. Comprehensive toxicological studies including genotoxicity and organ toxicity are limited. The compound is for research use only and is not approved as a therapeutic agent.
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| References | |
| Additional Infomation |
It has anti-HIV-1 activity
Dimethylamiloride (CAS# 1214-79-5) is a specific Na⁺/H⁺ exchanger (NHE) inhibitor with the molecular formula C₈H₁₂ClN₇O and a molecular weight of 257.68. It is a potent inhibitor of NHE1 (Ki = 0.02 μM), NHE2 (Ki = 0.25 μM), and NHE3 (Ki = 14 μM). Dimethylamiloride is used in research to study the role of Na⁺/H⁺ exchange in intracellular pH regulation, cell proliferation, cardiac ischemia, and cancer. The compound is also known as DMA and is available for research use only. As of current knowledge, Dimethylamiloride is not approved as a therapeutic agent. |
| Molecular Formula |
C8H12CLN7O
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|---|---|
| Molecular Weight |
257.68
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| Exact Mass |
293.056
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| CAS # |
1214-79-5
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| Related CAS # |
Dimethylamiloride hydrochloride;2235-97-4
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| PubChem CID |
1793
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.68g/cm3
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| Boiling Point |
543.6ºC at 760mmHg
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| Melting Point |
216-217°C(lit.)
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| Flash Point |
282.5ºC
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| Vapour Pressure |
7.08E-12mmHg at 25°C
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| Index of Refraction |
1.725
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| LogP |
1.975
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
317
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| Defined Atom Stereocenter Count |
0
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| SMILES |
NC1=NC(N(C)C)=C(Cl)N=C1C(N/C=N/N)=O
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| InChi Key |
RXMUPNVSYKGKMY-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C8H12ClN7O/c1-16(2)6-4(9)13-3(5(10)14-6)7(17)15-8(11)12/h1-2H3,(H2,10,14)(H4,11,12,15,17)
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| Chemical Name |
3-amino-6-chloro-N-(diaminomethylidene)-5-(dimethylamino)pyrazine-2-carboxamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8808 mL | 19.4039 mL | 38.8078 mL | |
| 5 mM | 0.7762 mL | 3.8808 mL | 7.7616 mL | |
| 10 mM | 0.3881 mL | 1.9404 mL | 3.8808 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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