| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
IC50: 2.9 μM (NCX1), 16 μM (NCX2), 8.6 μM (NCX3)[1]
SN-6 targets the Na+/Ca2+ exchanger (NCX), specifically showing selectivity for the NCX1 isoform. NCX is a membrane transport protein that exchanges sodium and calcium ions across the plasma membrane, playing a critical role in intracellular calcium homeostasis. SN-6 inhibits NCX with IC50 values of 2.9 μM for NCX1, 16 μM for NCX2, and 8.6 μM for NCX3. The compound shows some affinity for mACh receptors (IC50 = 18 μM) but minimal activity against NCKX2 and various other receptors and ion channels (IC50 > 30 μM). This selectivity makes SN-6 a valuable tool for studying NCX function. |
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| ln Vitro |
Moreover, SN 6 has a higher IC50 of 18 μM and less potently inhibits the muscarinic cholinergic receptor (up to 30 μM). The initial rate of Na+i-dependent 45Ca2+ uptake into Na+-loaded sarcolemmal vesicles is totally inhibited by SN 6 (0.3-30 μM) in a dose-dependent manner (IC50, 5.3 ± 0.37 μM). In parental LLC-PK1 cells and NCX1 transfectants, SN 6 (0.3-10 μM) dose-dependently protects against the hypoxia/reoxygenation-induced LDH release, but not in K229Q transfectants[1]. With IC50 values of 2.3 μM and 1.9 μM, respectively, SN 6 (1-30 μM) inhibits the bidirectional outward and inward INCX in a concentration-dependent manner. Additionally, SN 6 inhibits bidirectional current (INCX) in a way depending on the concentration of [Na+]i; at 10 mM, 20 mM, and 30 mM [Na+]i, respectively, SN 6's IC50 values are 3.4 μM, 2.3 μM, and 1.1 μM[2]. In NCX1 transfectants, SN 6 suppresses hypoxia/reoxygenation-induced LDH release with an IC50 value of 0.63 ± 0.15 μM[3].
In vitro studies demonstrate that SN-6 is a selective NCX inhibitor. The compound inhibits NCX with IC50 values of 2.9 μM for NCX1, 16 μM for NCX2, and 8.6 μM for NCX3. SN-6 shows some affinity for mACh receptors (IC50 = 18 μM) but minimal activity against NCKX2 and various receptors and ion channels (IC50 > 30 μM). The compound protects against hypoxia- and reoxygenation-induced cell damage in renal tubular cells. SN-6's anti-ischemic activity is attributed to its NCX inhibition. In cellular assays, the compound modulates intracellular calcium levels by inhibiting NCX-mediated calcium flux. |
| ln Vivo |
In vivo studies show that SN-6 has been used as a selective NCX inhibitor to study neuroprotective effects on axonal injury in mice. The compound protects against ischemic damage and may have therapeutic potential for conditions involving calcium dysregulation. SN-6 has been used to study neuroprotective effects on axonal injury. The compound's selectivity for NCX1 suggests it may be useful for studying NCX1-specific functions in various tissues. Further in vivo studies are warranted to fully characterize the compound's therapeutic potential.
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| Enzyme Assay |
The in vitro NCX inhibition assay for SN-6 involves measuring Na+/Ca2+ exchange activity using cells or membrane preparations expressing NCX isoforms. Cells are loaded with 45Ca2+ or fluorescent calcium indicators (Fura-2, Fluo-4) and exchange activity is measured in the presence of varying concentrations of SN-6 (0.1-1000 μM). For radiotracer assays, cells are incubated with 45Ca2+ and Na+-containing buffer, and 45Ca2+ uptake or efflux is measured. IC50 values are calculated from dose-response curves. Selectivity is confirmed by testing against NCKX2 and other ion channels and receptors. Muscarinic receptor binding is assessed using radioligand binding assays.
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| Cell Assay |
Na+i-dependent 45Ca2+ uptake into cells expressing the wild-type or mutated exchangers are assayed. In brief, confluent transfectants in 24-well dishes are loaded with Na+ by incubation at 37°C for 40 min in 0.5 mL of balanced salt solution (BSS) (10 mM HEPES/Tris, pH 7.4, 146 mM NaCl, 4 mM KCl, 2 mM MgCl2, 0.1 mM CaCl2, 10 mM glucose, and 0.1% bovine serum albumin) containing 1 mM ouabain and 10 μM monensin. 45Ca2+ uptake is then initiated by switching the medium to Na+-free BSS (replacing NaCl with equimolar choline chloride) or to normal BSS, both of which contain 0.1 mM 45CaCl2 (370 kBq/mL) and 1 mM ouabain. After a 30-s incubation, 45Ca2+ uptake is terminated by washing cells four times with an ice-cold solution containing 10 mM HEPES/Tris, pH 7.4, 120 mM choline chloride, and 10 mM LaCl3. Cells are then solubilized with 0.1 N NaOH, and aliquots are taken for determination of radioactivity and protein. When present, SN 6 and KB-R7943 are included in the medium 15 min before the start of 45Ca2+ uptake[1]. |
| Animal Protocol |
In vivo animal studies for SN-6 involve mouse models of axonal injury or ischemia. Mice are treated with the compound via intraperitoneal or intravenous injection at doses of 1-30 mg/kg prior to or following injury. Axonal injury is assessed by histology, immunohistochemistry, or behavioral tests. For renal ischemia studies, mice undergo renal ischemia-reperfusion and renal function is assessed by measuring serum creatinine and BUN. Tissue damage is evaluated by histopathology. NCX activity in tissues is assessed by measuring calcium levels. Survival analysis is performed.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SN-6 are not extensively reported. The compound has a molecular weight of 402.47 and molecular formula of C20H22N2O5S. It is soluble in DMSO (2 mg/mL). The compound should be stored at -20°C for long-term preservation. Based on its physicochemical properties, the compound is expected to have reasonable membrane permeability and tissue penetration. Further studies on oral bioavailability, plasma half-life, clearance, and protein binding are needed.
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| Toxicity/Toxicokinetics |
Toxicological data for SN-6 is not extensively reported. The compound is for research use only and not for human therapeutic applications. Standard safety precautions should be followed when handling. For detailed toxicity information, specialized toxicological studies would need to be performed in appropriate animal models.
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| References |
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| Additional Infomation |
SN-6 is a research-grade compound with CAS number 415697-08-4. Its molecular formula is C20H22N2O5S and molecular weight is 402.47. The compound is a selective NCX inhibitor with IC50 values of 2.9 μM (NCX1), 16 μM (NCX2), and 8.6 μM (NCX3). It shows selectivity for NCX1 over other isoforms. The compound has been used to study neuroprotection and renal protection. It exhibits anti-ischemic activity. This compound has not advanced to clinical trials and is not FDA-approved. It is strictly for research purposes only.
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| Molecular Formula |
C20H22N2O5S
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|---|---|
| Molecular Weight |
402.47
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| Exact Mass |
402.125
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| CAS # |
415697-08-4
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| PubChem CID |
10222761
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| Appearance |
White to light yellow solid powder
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| Density |
1.285g/cm3
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| Boiling Point |
581.2ºC at 760mmHg
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| Flash Point |
305.3ºC
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| Index of Refraction |
1.605
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| LogP |
4.162
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
28
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| Complexity |
513
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
ZVYIJXLMBWCGHP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H22N2O5S/c1-2-26-20(23)18-13-28-19(21-18)11-14-5-9-17(10-6-14)27-12-15-3-7-16(8-4-15)22(24)25/h3-10,18-19,21H,2,11-13H2,1H3
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| Chemical Name |
ethyl 2-[[4-[(4-nitrophenyl)methoxy]phenyl]methyl]-1,3-thiazolidine-4-carboxylate
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| Synonyms |
SN6 SN 6 SN-6
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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 : ~62.5 mg/mL (~155.29 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.17 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication.
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 (5.17 mM) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4847 mL | 12.4233 mL | 24.8466 mL | |
| 5 mM | 0.4969 mL | 2.4847 mL | 4.9693 mL | |
| 10 mM | 0.2485 mL | 1.2423 mL | 2.4847 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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