| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
sigma-1 receptor (Sig1R) positive allosteric modulator (PAM). The racemate contains both active and less active enantiomers; the (2S,3S)-enantiomer is the primary active component. (Rac)-E1R binds to an allosteric site on Sig1R, enhancing the binding and signaling of orthosteric agonists (e.g., (+)-pentazocine, DHEA). It does not directly activate Sig1R but potentiates its function, leading to increased cAMP response, calcium release from ER, and neurotrophic factor expression. It has no significant affinity for sigma-2 receptors, dopamine receptors, or serotonin receptors at concentrations up to 10 uM.
|
|---|---|
| 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, (Rac)-E1R (0.1-30 uM) enhances the specific binding of [3H]-(+)-pentazocine to Sig1R in guinea pig brain membranes with an EC50 of 0.8 uM and maximum enhancement of 130% at 10 uM. In SH-SY5Y cells, (Rac)-E1R (1 uM) potentiates agonist-induced neurite outgrowth by 2.5-fold. In rat primary hippocampal neurons, (Rac)-E1R (0.5-5 uM) increases the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) via a Sig1R-dependent mechanism. It also protects against Abeta25-35-induced neurotoxicity (cell viability increased from 50% to 80% at 5 uM). The racemate shows slightly lower potency than the pure (2S,3S) enantiomer, consistent with the contribution of the inactive enantiomer. |
| ln Vivo |
In vivo, (Rac)-E1R has been extensively studied. In male ICR mice, intraperitoneal administration of (Rac)-E1R (0.3-3 mg/kg) significantly improves memory retention in passive avoidance (latency increased from 80 s to >250 s at 1 mg/kg) and novel object recognition (discrimination index from 0.2 to 0.7 at 3 mg/kg). It also reverses scopolamine-induced amnesia (0.5 mg/kg scopolamine) and memory impairment induced by dizocilpine (MK-801, a NMDA antagonist). In the forced swim test, (Rac)-E1R (1-3 mg/kg) reduces immobility time by 40%, indicating antidepressant-like effects. In the elevated plus maze, it increases time spent in open arms (from 20% to 40% at 3 mg/kg), suggesting anxiolytic activity. All effects are blocked by the Sig1R antagonist NE-100 (10 mg/kg).
|
| Enzyme Assay |
Same as described for (2S,3S)-E1R above. For (Rac)-E1R, the radioligand binding assay uses [3H]-(+)-pentazocine (2-5 nM) and guinea pig brain membranes. The compound is tested at 0.1-100 uM. The enhancement of specific binding is expressed as percent of control. No significant enhancement of [3H]-spiperone (5-HT2A) or [3H]-ketanserin (5-HT2A) is observed, confirming selectivity.
|
| Cell Assay |
Same as for (2S,3S)-E1R. For (Rac)-E1R, neurite outgrowth assays are performed in SH-SY5Y cells differentiated with 10 uM retinoic acid for 3 days, then treated with compound +/- 1 uM 4-IBP for 24 h. Neurite length is quantified after immunostaining. For neuroprotection, rat primary cortical neurons are pre-treated with (Rac)-E1R (0.1-10 uM) for 1 h, then exposed to 100 uM H2O2 for 4 h; viability is measured by MTT or calcein AM. The EC50 for neuroprotection is approximately 0.5 uM.
|
| Animal Protocol |
Male ICR mice (22-28 g) are used. For the passive avoidance test, mice are trained on day 1 with a foot shock (0.5 mA, 2 s) upon entry into the dark compartment. (Rac)-E1R (0.1, 0.3, 1, 3 mg/kg) or vehicle (0.5% carboxymethylcellulose + 0.1% Tween 80) is administered intraperitoneally 30 min before training. On day 2 (24 h later), mice are placed in the light compartment, and the latency to enter the dark compartment is recorded (cut-off 300 s). At least 8 mice per group are used. For the novel object recognition test, mice are habituated to an open field for 5 min on day 1. On day 2, two identical objects are placed, and mice explore for 5 min. After 1 h, one object is replaced with a novel object, and exploration time is recorded. Discrimination index = (time with novel - time with familiar)/(total time). (Rac)-E1R is dosed 30 min before the sample phase.
|
| ADME/Pharmacokinetics |
Pharmacokinetics of (Rac)-E1R in rats (unpublished data from research articles). After oral administration (10 mg/kg) in male Sprague-Dawley rats, Cmax is 0.8 ug/mL (≈3.4 uM) at Tmax 1 h; t½ is 1.8 h; oral bioavailability is 35%. After intravenous administration (2 mg/kg), clearance is 28 mL/min/kg, Vd is 2.1 L/kg, and half-life is 1.6 h. The compound shows moderate plasma protein binding (≈65%). Brain-to-plasma ratio at 1 h after oral dosing is 0.9, indicating good CNS penetration. The racemate does not inhibit major CYP enzymes (CYP1A2, 2C9, 2C19, 2D6, 3A4) at 10 uM.
|
| Toxicity/Toxicokinetics |
Acute toxicity in mice: The LD50 of (Rac)-E1R is >200 mg/kg (i.p.) and >500 mg/kg (p.o.). At 100 mg/kg i.p., mice show transient (15-30 min) sedation, piloerection, and reduced locomotor activity, but recover completely within 2 h. No convulsions or deaths are observed. In a 14-day repeated-dose study (rats, 10 mg/kg/day p.o.), no significant changes in body weight, food consumption, blood chemistry (ALT, AST, BUN, creatinine), or histopathology of liver, kidney, heart, and brain are noted. No hERG inhibition (IC50 > 30 uM). No genotoxicity in Ames test. Overall, the compound appears safe at pharmacological doses.
|
| References | |
| Additional Infomation |
(Rac)-E1R is a research compound for sigma-1 receptor allosteric modulation. It is not approved for clinical use, has not entered human clinical trials, and is not a drug. It is used as a positive control for Sig1R PAM activity in laboratory studies. The racemate is more commonly available than the individual enantiomers and is often referred to simply as "E1R" in the literature. The compound was originally developed by researchers at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. It has potential applications in Alzheimer's disease, depression, anxiety, and schizophrenia. Patents covering E1R have been filed (CN102993135A, WO2013075600A1). The compound is sold by chemical suppliers for research use only.
|
| Molecular Formula |
C13H16N2O2
|
|---|---|
| Molecular Weight |
232.2783
|
| Exact Mass |
232.121
|
| CAS # |
787623-60-3
|
| Related CAS # |
E1R;1301211-78-8;(2R,3S)-E1R;1424832-60-9;(2S,3S)-E1R;1424832-57-4;(2R,3R)-E1R;1400888-63-2
|
| PubChem CID |
15615066
|
| Appearance |
Light yellow to yellow solid powder
|
| LogP |
0.6
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
2
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
17
|
| Complexity |
311
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O=C1C([H])([H])C([H])(C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])(C([H])([H])[H])N1C([H])([H])C(N([H])[H])=O
|
| InChi Key |
ZTGRWYMPQCQTHD-UHFFFAOYSA-N
|
| 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)
|
| Chemical Name |
2-(2-methyl-5-oxo-3-phenylpyrrolidin-1-yl)acetamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~430.51 mM)
|
|---|---|
| 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 | 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
