| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
Sigma 1 Receptor 0.93 nM (Ki) Sigma 2 Receptor 72 nM (Ki)
sigma-1 receptor (S1R). S1R agonist 1 is a selective S1R agonist with Ki values of 0.93 nM for S1R and 72 nM for S2R (sigma-2 receptor), demonstrating excellent selectivity for sigma-1 over sigma-2 (approximately 77-fold selectivity). |
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| ln Vitro |
In PC12 cells, nerve growth factor (NGF)-induced neurite outgrowth can be markedly enhanced in a dose-dependent manner by S1R agonist 1 (Compound 6b; 0.1-5 μM) [1]. At a dosage of 1 μM, S1R agonist 1 (24 h) significantly inhibits the harm that Rotenone causes to SHSY5Y cells. Neuroprotective effects of S1R agonist 1 (0.1-5 μM; 24 h) on NMDA activation in SHSY5Y cells [1]. A549, LoVo, and Panc-1 cells are not cytotoxic when exposed to S1R agonist 1 (0–10 μM; 24-72 h) [1].
S1R agonist 1 has Ki values of 0.93 nM for sigma-1 receptor and 72 nM for sigma-2 receptor, demonstrating significant selectivity for sigma-1. It exhibits neuroprotection against ROS- and NMDA-induced neurotoxicity. At concentrations of 0.1-5 uM, it significantly increases nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells in a dose-dependent manner. At 1 uM (24 h), it significantly inhibits rotenone-induced cell damage in SH-SY5Y cells. |
| ln Vivo |
At 10 μM, S1R agonist 1 (Compound 6b; 0.1-50 μM; 120 h) killed 4 of the 8 zebrafish embryos [1].
In PC12 cells, S1R agonist 1 (0.1-5 uM) significantly increases NGF-induced neurite outgrowth in a dose-dependent manner, suggesting a role in neuronal differentiation and repair. It provides neuroprotection against oxidative stress (ROS) and excitotoxicity (NMDA-induced neurotoxicity). The neuroprotective effects are mediated through sigma-1 receptor activation, which modulates calcium signaling and ER stress responses. |
| Enzyme Assay |
Cell-free sigma-1 receptor binding assays: Guinea pig brain membranes are prepared and incubated with [3H]-pentazocine (1-5 nM) and increasing concentrations of S1R agonist 1 (0.001-10,000 nM) in 50 mM Tris-HCl, pH 8.0, containing 100 mM NaCl for 120 min at 25degC. Bound radioactivity is separated by GF/B filtration. Ki values are calculated using the Cheng-Prusoff equation. For sigma-2 binding, rat liver membranes and [3H]-DTG in the presence of (+)pentazocine are used. Ki(S1R) = 0.93 nM, Ki(S2R) = 72 nM.
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| Cell Assay |
PC12 cells (rat pheochromocytoma) are cultured and treated with S1R agonist 1 (0.1-5 uM) in the presence of NGF (50 ng/mL) for 48-72 hours. Neurite outgrowth is quantified by microscopy and image analysis. For neuroprotection assays, SH-SY5Y human neuroblastoma cells are pre-incubated with S1R agonist 1 (0.1-10 uM) for 2 hours, then exposed to rotenone (0.1-1 uM, 24 h) or NMDA (100 uM, 24 h) or ROS-generating agents. Cell viability is assessed by MTT or LDH release assay. S1R agonist 1 (1 uM) significantly inhibits rotenone-induced cell damage.
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| Animal Protocol |
In vivo neuroprotection studies are typically conducted in rodent models of neurodegenerative disease (e.g., MPTP model of Parkinson‘s disease, NMDA-induced excitotoxicity model, or middle cerebral artery occlusion model of stroke). S1R agonist 1 is administered intraperitoneally (1-10 mg/kg) or orally 30 min prior to insult. Neurobehavioral outcomes (rotarod, grip strength) are assessed, and brain tissue is collected for histology (TUNEL, NeuN staining) and biochemical analysis (oxidative stress markers). No specific published animal protocols are available for this compound.
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| ADME/Pharmacokinetics |
No specific PK data are reported for S1R agonist 1. As a selective sigma-1 receptor agonist, it is expected to be brain-penetrant, as sigma-1 receptors are extensively expressed in the CNS. Molecular weight and LogP suggest moderate oral bioavailability. Recommended storage: -20degC, protect from light. Solubility: DMSO (50-100 mg/mL). Standard PK parameters (t1/2, Cmax, AUC, F%) have not been determined.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for S1R agonist 1. In vitro studies at concentrations up to 10 uM show no overt cytotoxicity in PC12 or SH-SY5Y cells. The neuroprotective effects against rotenone- and NMDA-induced toxicity indicate a favorable safety profile at active concentrations. Standard safety assessments would include hERG channel inhibition and Ames test. No clinical trials have been conducted.
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| References | |
| Additional Infomation |
Other information: S1R agonist 1 (compound 6b) is a research chemical, not FDA-approved. It is a selective sigma-1 receptor agonist with high affinity (Ki = 0.93 nM) and significant selectivity over sigma-2 (approximately 77-fold selectivity). CAS number: 193354-70-0. The compound is being studied for Alzheimer‘s disease and neuropathic pain. It modulates calcium signaling and ER stress. It is for research use only.
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| Molecular Formula |
C20H25NO
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|---|---|
| Molecular Weight |
295.42
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| Exact Mass |
295.194
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| CAS # |
193354-70-0
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| Related CAS # |
S1R agonist 1 hydrochloride;242487-82-7
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| PubChem CID |
1328600
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| Appearance |
Colorless to light yellow liquid
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
22
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| Complexity |
286
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCC1CC2=CC=CC=C2)CCOC3=CC=CC=C3
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| InChi Key |
HRBKFQYSVXXYDE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25NO/c1-3-7-18(8-4-1)17-19-11-13-21(14-12-19)15-16-22-20-9-5-2-6-10-20/h1-10,19H,11-17H2
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| Chemical Name |
4-benzyl-1-(2-phenoxyethyl)piperidine
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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 | 3.3850 mL | 16.9251 mL | 33.8501 mL | |
| 5 mM | 0.6770 mL | 3.3850 mL | 6.7700 mL | |
| 10 mM | 0.3385 mL | 1.6925 mL | 3.3850 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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