| Size | Price | Stock | Qty |
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| Targets |
NHE3-IN-2 specifically targets NHE3 (sodium-hydrogen exchanger 3). NHE3 is a membrane protein located on the apical (luminal) side of intestinal and renal epithelial cells. It functions as an exchanger, moving one sodium ion into the cell in exchange for one hydrogen ion (proton) out of the cell. This process is essential for the absorption of sodium and water. By inhibiting NHE3, NHE3-IN-2 reduces sodium and fluid reabsorption, which leads to increased sodium and water excretion (natriuresis and diuresis). This mechanism helps lower blood pressure and reduce plasma volume..
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| ln Vitro |
Specific in vitro activity data for NHE3-IN-2 is not provided in the search results. It is described as an inhibitor of NHE3 (Na+/H+ exchanger-3). Its activity is defined by its ability to block the exchange of extracellular sodium for intracellular hydrogen ions. The mechanism is competitive inhibition, typically measured in an in vitro assay using cells expressing NHE3.
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| ln Vivo |
Specific in vivo activity data for NHE3-IN-2 is not detailed in the provided search results. As an NHE3 inhibitor, it is hypothesized to lower blood pressure in animal models of hypertension (e.g., spontaneously hypertensive rats, SHR) by inducing sodium and water excretion. By blocking NHE3 in the kidney, the compound reduces sodium reabsorption, leading to a diuretic effect and a reduction in blood pressure. It may also have applications in models of heart failure and chronic kidney disease. The compound is applicable for treating hypertension, thrombosis, and ischaemic diseases..
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| Enzyme Assay |
The standard in vitro protocol for assessing NHE3 inhibition is a fluorescence-based or radiolabeled sodium uptake assay using cells expressing NHE3. HEK-293 or PS120 fibroblasts (which lack endogenous NHE activity) are stably transfected with human NHE3. Cells are seeded in 96-well plates and grown to confluency. The medium is then replaced with a sodium-free buffer (to acidify the cytoplasm and activate the exchanger). Varying concentrations of NHE3-IN-2 (0.01-100 uM) are added to the cells and pre-incubated for 10 minutes. To measure activity, a sodium-containing buffer (e.g., 5 mM NaCl) containing a fluorescent sodium indicator (e.g., SBFI-AM, sodium-binding benzofuran isophthalate) or [22Na] (radiolabeled sodium) is added to the cells. The rate of sodium influx, reflected by an increase in fluorescence or radioactivity, is monitored. The IC50 is calculated from the inhibition curve.
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| Cell Assay |
The in vitro cellular assay for NHE3-IN-2 involves the use of human intestinal epithelial cells (e.g., Caco-2 cells) that endogenously express high levels of NHE3 on the apical surface. Cells are seeded on 24-mm Transwell permeable filters and cultured for 21 days to form a polarized monolayer (enterocyte-like phenotype). The filters are mounted in Ussing chambers. Both the apical and basolateral sides are bathed in Ringers solution. A pH-sensitive electrode or a pH-stat is used to measure H+ efflux (or the rate of Na+ absorption). The monolayer is voltage-clamped. NHE3-IN-2 is added to the apical side. A decrease in the short-circuit current (Isc) or a reduction in the rate of acid secretion indicates NHE3 inhibition. Varying concentrations of the compound (0.1-1000 nM) are added to calculate the IC50.
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| Animal Protocol |
An in vivo protocol for NHE3-IN-2 would involve a spontaneously hypertensive rat (SHR) model of hypertension. Male SHR (8-10 weeks old, 200-250 g) are housed in metabolic cages for 24-hour urine collection. NHE3-IN-2 is formulated in a suitable vehicle (e.g., 0.5% methylcellulose) and administered orally by gavage at doses of 1, 3, 10, and 30 mg/kg once daily for 4 weeks. Blood pressure is measured weekly by tail-cuff plethysmography. Urine volume and urinary sodium excretion (measured by flame photometry) are quantified from the metabolic cages. At the end of the study, blood samples are collected to measure serum electrolytes (Na+, K+, Cl-) and BUN/creatinine to assess renal function. The compound would be expected to lower blood pressure and increase urinary sodium and water excretion in a dose-dependent manner.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) data for NHE3-IN-2 is not provided. As a small molecule with a molecular weight of 297.74 g/mol, it is likely designed for oral administration. A standard PK study in rats would involve oral (PO) administration (10 mg/kg) and intravenous (IV) administration (1 mg/kg). Blood samples are collected at multiple time points (0-24 h), and plasma concentrations of the compound are quantified by LC-MS/MS. Key parameters, including terminal half-life (T1/2), maximum plasma concentration (Cmax), area under the curve (AUC), and oral bioavailability (F%), would be calculated. Since NHE3 is a local transporter in the gut and kidney, the compound may exhibit a high volume of distribution to these tissues.
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| Toxicity/Toxicokinetics |
Specific toxicological data for NHE3-IN-2 is not available. As an NHE3 inhibitor that blocks sodium reabsorption, the primary safety concerns are dehydration, electrolyte imbalances (hyponatremia, hyperkalemia, metabolic acidosis), and the potential for renal impairment. Standard safety assessment would include a 14-day repeat-dose oral toxicity study in rats to determine the Maximum Tolerated Dose (MTD) and the No-Observed-Adverse-Effect Level (NOAEL). Key endpoints would include monitoring of body weight, food and water consumption, urinalysis (volume, pH, electrolytes), and serum chemistry (comprehensive metabolic panel). Histopathological examination of the kidney and gastrointestinal tract would be crucial to assess for any structural damage.
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| References | |
| Additional Infomation |
2-(6-chloro-4-phenyl-2-quinazolinyl)guanidine is a member of the pyrimidine class of compounds.
I-Source: patent WO2001079186A1 (example 6-Chlor-4-phenyl-2-chinazolinyl-guanidin). NHE3-IN-2 is a research-grade chemical and is not approved for clinical use. It is an inhibitor of NHE3 (Na+/H+ exchanger 3), a major transporter responsible for sodium and water reabsorption in the gut and kidney. This compound is used in research as a tool to study the pathophysiology of hypertension, heart failure, and thrombosis. By inhibiting NHE3, it acts as a natriuretic and diuretic agent, helping to reduce plasma volume and lower blood pressure. It is for research use only. |
| Molecular Formula |
C15H12CLN5
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|---|---|
| Molecular Weight |
297.74
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| Exact Mass |
297.078
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| CAS # |
92434-13-4
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| PubChem CID |
3145916
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| Appearance |
Light yellow to green yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
552.7±42.0 °C at 760 mmHg
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| Flash Point |
288.1±27.9 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.725
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| LogP |
2.67
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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 |
2
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| Heavy Atom Count |
21
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| Complexity |
378
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC=C(C=C1)C2=NC(=NC3=C2C=C(C=C3)Cl)N=C(N)N
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| InChi Key |
RGJFEUSQLIFRJG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12ClN5/c16-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)20-15(19-12)21-14(17)18/h1-8H,(H4,17,18,19,20,21)
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| Chemical Name |
2-(6-chloro-4-phenylquinazolin-2-yl)guanidine
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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: 3.33 mg/mL (11.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.33 mg/mL (1.11 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 3.3 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: ≥ 0.33 mg/mL (1.11 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 3.3 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3586 mL | 16.7932 mL | 33.5864 mL | |
| 5 mM | 0.6717 mL | 3.3586 mL | 6.7173 mL | |
| 10 mM | 0.3359 mL | 1.6793 mL | 3.3586 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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