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Purity: ≥98%
Encenicline (EVP-6124; MT-4666) is a novel partial agonist of α7 nicotinic acetylcholine receptor. EVP-6124 enhances dopamine, acetylcholine, and glutamate efflux in rat cortex and nucleus accumbens. EVP-6124 improves memory performance by potentiating the acetylcholine response of α7 nicotinic acetylcholine receptors.
| ln Vitro |
Encenicline (EVP-6124) has been substituted for [3H]-MLA (methylaconitine) (Ki=9.98 nM, pIC50=7.65±0.06, n=3) and [125I]-α-bungarotoxin (Ki=4.33 nM, pIC50=8.07±0.04), n=3). By using a [3H]-MLA binding test, encenicline (EVP-6124) was found to be around 300 times more powerful than the natural agonist ACh (Ki=3 μM). At 10 nM, the lowest studied concentration, encenicline inhibits 5-HT3 receptors by 51%. An assessment of human 5-HT2B receptors produced in CHO cells revealed only antagonist action in the rat fundus assay, with an IC50 of 16 μM, and displacement of [3H]-mesoergot (Ki=14 nM). Encenicline exhibited selectivity for α7 nAChR in binding and functional tests, but it did neither inhibit or activate heteromeric α4β2 nAChR[1].
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| ln Vivo |
Encenicline (EVP-6124) exhibits adequate exposure duration and strong brain penetration. In rats treated with scopolamine (0.1 mg/kg, ip), encenicline (EVP-6124) (0.3 mg/kg, po) dramatically improved memory performance during the object recognition test (ORT). On this task, oral donepezil (0.1 mg/kg) or encenicline (0.03 mg/kg) did not improve memory; however, coadministration of these ineffective doses totally restored memory. During a 24-hour retention period, encenicline at 0.3 mg/kg, po, enhanced memory in the spontaneous forgetting test (ORT). Methylated aconitine (0.3 mg/kg, ip or 10 μg, icv), a specific α7 nAChR antagonist, prevented this improvement. With a mean fu of 0.11±0.01 (mean±SD), or 11%, encenicline (EVP-6124) was shown to be moderately bound to rat plasma proteins. Proportionate dose escalation is seen with encenicline (EVP-6124) over the 0.1–30 mg/kg oral dosing range. Tmax was 4 hours for plasma and 2 hours for the brain; however, the concentrations in the brain did not change between 2 and 8 hours. The B:P ratio is 1.7–5.1 during the first eight hours[1]. According to pharmacokinetic research, encenicline (EVP-6124) (0.4 mg/kg, intraperitoneal injection) achieves maximum brain concentrations two hours after injection and keeps these quantities useful for a minimum of four hours. Without producing extended wakefulness or increased locomotor activity, encenicline (EVP-6124) given to WT mice at ZT0 (0.4 mg/kg ip single dose) dramatically raised the saturation index of NMDAR in slices retrieved 4 hours later [ 2].
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| References |
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| Additional Infomation |
Encenicline has been investigated for the treatment of Cognition, Schizophrenia, Alzheimer's Disease, Cardiac Repolarization, and Central Nervous System Diseases.
Mechanism of Action Encenicline, a selective, orally active, alpha 7 Nicotinic Acetylcholine Receptor agonist (alpha 7 NAchR agonist). Encenicline may have a similar mechanism of action to GTS-21. Auditory sensory gating, a biological measurement of the ability to suppress the evoked response to the second of two auditory stimuli, is diminished in people with schizophrenia. Deficits in sensory gating are associated with attentional impairment, and may contribute to cognitive symptoms and perceptual disturbances. This inhibitory process, which involves the alpha(7) nicotinic receptor mediated release of gamma-aminobutyric acid (GABA) by hippocampal interneurons, represents a potential new target for therapeutic intervention in schizophrenia. |
| Molecular Formula |
C16H17CLN2OS
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|---|---|
| Molecular Weight |
320.84
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| Exact Mass |
320.075
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| CAS # |
550999-75-2
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| Related CAS # |
Encenicline hydrochloride;550999-74-1
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| PubChem CID |
46196517
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
3.707
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
413
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C(C1=CC2=C(C(Cl)=CC=C2)S1)N[C@H]3CN4CCC3CC4
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| InChi Key |
N-[(3R)-1-Azabicyclo[2.2.2]octan-3-yl]-7-chloro-1-benzothiophene-2-carboxamide
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| InChi Code |
SSRDSYXGYPJKRR-ZDUSSCGKSA-N
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| Chemical Name |
N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-7-chloro-1-benzothiophene-2-carboxamide
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| Synonyms |
EVP-6124 EVP6124 EVP 6124 MT-4666 MT4666 MT 4666 Encenicline
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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 | 3.1168 mL | 15.5841 mL | 31.1682 mL | |
| 5 mM | 0.6234 mL | 3.1168 mL | 6.2336 mL | |
| 10 mM | 0.3117 mL | 1.5584 mL | 3.1168 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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