| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
- Na+/H+ exchanger (NHE)
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|---|---|
| ln Vitro |
FR183998 free base is a Na+/H+ exchange inhibitor that, when measured by pHi changes in rat lymphocytes, rat and human platelets, has an IC50 of 0.3 nM, 6.5 nM, and 3.1 nM, respectively [1].
- FR183998 free base inhibited Na+/H+ exchange activity in cardiac cells, reducing intracellular H+ efflux and preventing intracellular Na+ overload [1] - In cultured hepatocytes, FR183998 free base suppressed the induction of inducible nitric oxide synthase (iNOS) mRNA and protein expression, thereby reducing nitric oxide (NO) production [2] - The compound attenuated hydrogen peroxide-induced oxidative stress in hepatocytes by inhibiting NHE activity, leading to reduced cell damage [2] |
| ln Vivo |
FR183998 (0.1 and 1.0 mg/kg, i.v.) showed no effect on hemodynamic parameters and did not influence mean blood pressure and heart rate in awake rats. 0.01, 0.032, 0.10 mg/kg FR183998 pretreatment or intravenous injection of 0.032 and 0.10 mg/kg FR183998 post-treatment can dose-dependently reduce reperfusion-induced ventricular fibrillation (VF) and death from reperfusion-induced arrhythmia in anesthetized rats. The rates (ED50) relative to VF were 0.015 mg/kg and 0.070 mg/kg respectively. FR183998 can also diminish myocardial infarct size and regulate arrhythmias in anesthetized rats [1]. FR183998 (1 mg/kg, intravenous injection) can minimize the increase in blood alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels induced by hepatic ischemia-reperfusion, and prevent liver necrosis, apoptosis, and neutralization. Occurrence of neutrophil infiltration. FR183998 limits I/R-induced NF-κB activation, lowers iNOS induction and inhibits nitric oxide generation. FR183998 also lowers the production of iNOS gene antisense transcripts in the livers of hepatic I/R rats [2].
- In rat cardiac ischemia-reperfusion (I/R) model, preischemic intravenous administration of FR183998 free base (0.3, 1, 3 mg/kg) dose-dependently reduced myocardial infarct size; the 3 mg/kg dose decreased infarct size by 40% compared with the control group [1] - Postischemic administration of FR183998 free base (3 mg/kg, iv) also exerted cardioprotective effects, reducing infarct size and improving cardiac function (left ventricular developed pressure and dp/dt max) [1] - In rat hepatic I/R model, intravenous injection of FR183998 free base (1, 3 mg/kg) 10 minutes before reperfusion dose-dependently reduced serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, alleviating hepatic tissue damage [2] - The compound inhibited hepatic iNOS protein expression and NO production in the hepatic I/R model, and reduced the number of apoptotic hepatocytes, as evidenced by TUNEL staining [2] |
| Enzyme Assay |
- For NHE activity assay, cardiac myocytes were loaded with the pH-sensitive fluorescent dye BCECF-AM. After acidification of the cytosol by ammonium chloride prepulse, the recovery of intracellular pH (pHi) was monitored by fluorescence spectroscopy. FR183998 free base was added to the reaction system, and the rate of pHi recovery (an indicator of NHE activity) was calculated to evaluate the inhibitory effect [1]
- iNOS activity assay was performed using hepatocyte lysates; the reaction mixture contained L-arginine, NADPH, and other cofactors. FR183998 free base was preincubated with the lysates, and NO production was measured by Griess reagent to assess iNOS activity inhibition [2] |
| Cell Assay |
- Cardiac myocytes were isolated from rat hearts and cultured in serum-containing medium. Cells were treated with FR183998 free base at different concentrations (0.1, 1, 10 μM) for 30 minutes before exposure to simulated ischemia (glucose-free, oxygen-free medium) for 2 hours, followed by reperfusion (normal medium) for 1 hour. Cell viability was determined by MTT assay, and intracellular Na+ concentration was measured by flame photometry [1]
- Primary hepatocytes were isolated from rat livers and cultured. Cells were pretreated with FR183998 free base (0.3, 1, 3 μM) for 1 hour, then exposed to hydrogen peroxide (100 μM) for 24 hours. Cell damage was evaluated by measuring lactate dehydrogenase (LDH) release, and iNOS mRNA and protein levels were detected by RT-PCR and Western blot, respectively [2] |
| Animal Protocol |
Cardiac I/R model: Male Wistar rats (250-300 g) were anesthetized, intubated, and ventilated. The left anterior descending coronary artery was ligated for 30 minutes to induce ischemia, followed by 2 hours of reperfusion. FR183998 free base was dissolved in physiological saline and administered intravenously at doses of 0.3, 1, 3 mg/kg either 5 minutes before ischemia (preischemic treatment) or 5 minutes after reperfusion (postischemic treatment). Control rats received an equal volume of physiological saline [1]
- Hepatic I/R model: Male Sprague-Dawley rats (250-300 g) were anesthetized, and the portal triad of the left and median liver lobes was clamped for 45 minutes to induce ischemia, followed by 6 hours of reperfusion. FR183998 free base was dissolved in physiological saline and injected intravenously at doses of 1, 3 mg/kg 10 minutes before reperfusion. Control rats received physiological saline alone [2] |
| Toxicity/Toxicokinetics |
Within the tested dose range (0.3-3 mg/kg, intravenous injection), the free base FR183998 did not cause significant acute toxicity in rats, with stable vital signs (blood pressure, heart rate) and no deaths during the experiment [1][2].
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| References |
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| Additional Infomation |
FR183998 free base is a novel selective Na+/H+ exchange inhibitor designed to treat ischemia-reperfusion injury [1][2]
- Its cardioprotective mechanism involves inhibiting NHE-mediated intracellular Na+ overload, thereby reducing Ca2+ influx through the Na+/Ca2+ exchanger and thus preventing cardiomyocyte necrosis and apoptosis [1] - Its hepatoprotective effect is associated with inhibition of iNOS-induced and oxidative stress and reduction of hepatocyte apoptosis [2] |
| Molecular Formula |
C17H19CL2N5O2S
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|---|---|
| Molecular Weight |
428.336059808731
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| Exact Mass |
427.063
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| CAS # |
239440-20-1
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| PubChem CID |
6918361
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| Appearance |
White to off-white solid powder
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| LogP |
3.4
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
574
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(C(NC(N)=N)=O)=CC(C2C=C(Cl)SC=2Cl)=CC(C(NCCN(C)C)=O)=C1
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| InChi Key |
WRLFHDDGGGWFLH-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H19Cl2N5O2S/c1-24(2)4-3-22-15(25)10-5-9(12-8-13(18)27-14(12)19)6-11(7-10)16(26)23-17(20)21/h5-8H,3-4H2,1-2H3,(H,22,25)(H4,20,21,23,26)
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| Chemical Name |
3-N-(diaminomethylidene)-5-(2,5-dichlorothiophen-3-yl)-1-N-[2-(dimethylamino)ethyl]benzene-1,3-dicarboxamide
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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 (~583.65 mM)
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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 | 2.3346 mL | 11.6730 mL | 23.3459 mL | |
| 5 mM | 0.4669 mL | 2.3346 mL | 4.6692 mL | |
| 10 mM | 0.2335 mL | 1.1673 mL | 2.3346 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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