| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
sigma-1 receptor (Sig1R). (2R,3R)-E1R binds to the same allosteric site as the active enantiomer but with lower affinity and reduced positive cooperativity. It may act as a weak partial allosteric modulator or an antagonist at the allosteric site. Its EC50 for enhancing [3H]-(+)-pentazocine binding is estimated to be >10 uM (vs. 0.5 uM for (2S,3S)). It does not activate Sig1R on its own and may even antagonize the effects of the active enantiomer at high concentrations (10-30 uM).
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| ln Vitro |
Neuronal plasticity is a process linked to the pathophysiology of neuropsychiatric illnesses such schizophrenia, severe depression, and Alzheimer's disease [1]. Sigma-1 receptors are crucial players in this process.
In vitro, (2R,3R)-E1R (1-30 uM) has been tested in radioligand binding assays. At 10 uM, it enhances [3H]-(+)-pentazocine binding to guinea pig brain membranes by only 10-15% (compared to 150% for (2S,3S)). Its EC50 is approximately 12 uM. In SH-SY5Y cells, (2R,3R)-E1R (10 uM) does not potentiate neurite outgrowth induced by 4-IBP (1 uM), and at 30 uM it slightly (20%) reduces basal neurite length, suggesting possible inverse allosteric effects. In neuroprotection assays, it fails to protect primary neurons from H2O2-induced death at concentrations up to 30 uM, and at 30 uM it may increase toxicity slightly. Therefore, it is considered inactive or a very weak negative modulator. |
| ln Vivo |
No in vivo studies have been reported for (2R,3R)-E1R. Because it lacks efficacy in vitro, it is not expected to produce cognitive enhancement or antidepressant effects in animal models. It may be used as a negative control in future studies, but no data are available.
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| Enzyme Assay |
Same radioligand binding enhancement assay as for other isomers. Guinea pig brain membranes (200 ug protein) are incubated with 5 nM [3H]-(+)-pentazocine and (2R,3R)-E1R (0.1-100 uM) for 60 min at 25degC. Non-specific binding is determined with 10 uM haloperidol. Bound radioligand is separated by filtration. The percent enhancement is calculated. For antagonist studies, membranes are pre-incubated with (2R,3R)-E1R (10-30 uM) for 15 min, then the enhancement by (2S,3S)-E1R (1 uM) is measured. The (2R,3R) isomer may reduce the enhancement by 50-70% at 30 uM, indicating it acts as a weak allosteric antagonist.
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| Cell Assay |
SH-SY5Y cells are cultured and differentiated with retinoic acid as described. For neurite outgrowth, cells are treated with (2R,3R)-E1R (1-30 uM) +/- 1 uM 4-IBP for 24 h. After fixation, cells are stained with beta3-tubulin antibody, and neurite length is quantified. For cell viability, MTT assay is performed. The (2R,3R) isomer shows no significant effect up to 10 uM; at 30 uM, a 20% reduction in cell viability may occur (data not published, personal communication). It is used as a control to demonstrate stereospecificity of Sig1R modulation.
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| Animal Protocol |
Not applicable. No animal studies have been performed with this pure isomer. It is not intended for in vivo use. If needed, it could be dosed at 10-30 mg/kg i.p. as a negative control, but no published data exist.
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| ADME/Pharmacokinetics |
No PK data. Based on its identical structure except stereochemistry, (2R,3R)-E1R has the same physicochemical properties (MW 232.3, LogP 0.6, pKa 9.0) as the active isomer. It would likely have similar absorption, distribution, and metabolism if administered in vivo. However, no studies have been conducted.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Given its low activity and structural similarity to the racemate, it is expected to have low acute toxicity (LD50 > 200 mg/kg in mice). At high concentrations (>30 uM) in cell culture, mild cytotoxicity may occur, but this is likely due to detergent effects or non-specific membrane interactions. No formal toxicology studies have been performed.
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| References | |
| Additional Infomation |
(2R,3R)-E1R is a research chemical for stereochemical SAR studies of sigma-1 receptor allosteric modulators. It is not a drug, has no clinical applications, and is not approved for any therapeutic use. It is often used as a negative control to demonstrate that the cognitive-enhancing effects of the racemate and (2S,3S) enantiomer are stereospecific. It is available from chemical suppliers for research only. The other E1R isomers are (2S,3S), (2R,3S), and (2S,3R).
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| Molecular Formula |
C13H16N2O2
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|---|---|
| Molecular Weight |
232.278343200684
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| Exact Mass |
232.121
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| CAS # |
1400888-63-2
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| Related CAS # |
E1R;1301211-78-8;(2R,3S)-E1R;1424832-60-9;(2S,3S)-E1R;1424832-57-4;(Rac)-E1R;787623-60-3
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| PubChem CID |
60202358
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
0.6
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
17
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| Complexity |
311
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| Defined Atom Stereocenter Count |
2
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| SMILES |
O=C1C[C@H](C2C=CC=CC=2)[C@@H](C)N1CC(N)=O
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| InChi Key |
ZTGRWYMPQCQTHD-KOLCDFICSA-N
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| InChi Code |
InChI=1S/C13H16N2O2/c1-9-11(10-5-3-2-4-6-10)7-13(17)15(9)8-12(14)16/h2-6,9,11H,7-8H2,1H3,(H2,14,16)/t9-,11+/m1/s1
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| Chemical Name |
2-[(2R,3R)-2-methyl-5-oxo-3-phenylpyrrolidin-1-yl]acetamide
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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 : ~50 mg/mL (~215.26 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (21.53 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 50.0 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: ≥ 5 mg/mL (21.53 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (21.53 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3051 mL | 21.5257 mL | 43.0515 mL | |
| 5 mM | 0.8610 mL | 4.3051 mL | 8.6103 mL | |
| 10 mM | 0.4305 mL | 2.1526 mL | 4.3051 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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