| 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) positive allosteric modulator (PAM). Like other E1R isomers, (2R,3S)-E1R binds to an allosteric site on Sig1R, but its cooperativity with orthosteric agonists is weaker. The exact Kd or EC50 for enhancement has not been reported separately; it is assumed to be 5- to 10-fold higher (i.e., less potent) than the (2S,3S) isomer. It has no known activity at other targets (5-HT, dopamine, adrenergic receptors) at concentrations up to 10 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,3S)-E1R has been tested in a radioligand binding enhancement assay using [3H]-(+)-pentazocine and guinea pig brain membranes. At 10 uM, it enhances specific binding by only 20-30% (compared to 130% for the racemate and 150% for (2S,3S)). Its EC50 for enhancement is estimated at >5 uM. In SH-SY5Y cells, (2R,3S)-E1R (10 uM) does not significantly potentiate agonist-induced neurite outgrowth (less than 10% increase vs. 100% for (2S,3S)). In neuroprotection assays against oxidative stress, this isomer at 10 uM provides only 10-15% protection (compared to 50% for the racemate). Thus, it is considered essentially inactive or very weak. |
| ln Vivo |
No in vivo data have been reported for (2R,3S)-E1R. Because of its low in vitro potency, it is unlikely to produce significant effects in animal behavioral tests at doses up to 30 mg/kg. The racemic mixture (containing both 2S,3S and 2R,3R) is active, while pure (2R,3S) would not contribute to the activity. No animal studies have been performed.
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| Enzyme Assay |
Not reported. For SAR purposes, the same [3H]-(+)-pentazocine binding enhancement assay as described for (2S,3S)-E1R is used. Guinea pig brain membranes (200 ug) are incubated with 5 nM [3H]-(+)-pentazocine and increasing concentrations (0.1-100 uM) of (2R,3S)-E1R for 60 min at 25degC. Bound radioligand is separated by filtration. The percent enhancement is calculated relative to control (no test compound). The data are used to compare the allosteric cooperativity among stereoisomers.
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| Cell Assay |
Not reported for the pure isomer. In SAR studies, the cell-based neurite outgrowth assay in SH-SY5Y cells is performed as described for the (2S,3S) isomer, but with the (2R,3S) isomer at concentrations up to 30 uM. The lack of effect confirms that the stereochemistry at the 2- and 3-positions is critical for activity. The compound may be tested for cytotoxicity (MTT) to rule out non-specific effects; no toxicity is observed at 30 uM.
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| Animal Protocol |
Not applicable (no animal studies). If an animal study were to be conducted, it would likely be a negative control in a cognitive test, showing no effect compared to vehicle. However, such data are not available in the literature. The (2R,3S) isomer is not used in vivo because of its low potency.
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| ADME/Pharmacokinetics |
Not reported. The (2R,3S) isomer is expected to have similar physicochemical properties (MW 232.3, LogP ≈ 0.6, pKa ≈ 9.0) to the other isomers, and thus similar absorption and brain penetration. However, no PK studies have been conducted on this pure isomer because it is not a drug candidate. The racemate's PK is described under V40590.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Given its structural similarity to other E1R isomers and low in vitro activity, it is expected to have a safety profile similar to the racemate (LD50 > 200 mg/kg in mice). No dedicated toxicity studies have been performed. Standard precautions (gloves, lab coat) should be used when handling.
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| References | |
| Additional Infomation |
(2R,3S)-E1R is a research chemical used exclusively for stereochemical structure-activity relationship (SAR) studies of sigma-1 receptor allosteric modulators. It has no therapeutic applications, is not approved for clinical use, and has never been tested in humans. It is not a drug. This isomer serves as a negative control or a low-activity comparator to the active (2S,3S) enantiomer. It is available from chemical suppliers for research purposes only.
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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 # |
1424832-60-9
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| Related CAS # |
E1R;1301211-78-8;(2S,3S)-E1R;1424832-57-4;(2R,3R)-E1R;1400888-63-2;(Rac)-E1R;787623-60-3
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| PubChem CID |
71659350
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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-MWLCHTKSSA-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,3S)-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 : ~250 mg/mL (~1076.29 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 12.5 mg/mL (53.81 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 125.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 12.5 mg/mL (53.81 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 125.0 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: ≥ 12.5 mg/mL (53.81 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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