| Size | Price | Stock | Qty |
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| 5mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Encenicline selectively targets and activates the α7 nicotinic acetylcholine receptor (nAChR). It displaces [³H]-MLA with a KF of 9.98 nM and [¹²⁵I]-α-bungarotoxin with a KF of 4.33 nM. It is approximately 300-fold more potent than the natural agonist ACh. In binding and functional experiments, encenicline shows selectivity for α7 nAChRs and does not activate or inhibit heteromeric α4β2 nAChRs. It also inhibits the 5-HT₃ receptor by 51% at 10 nM.
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| 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].
In vitro, encenicline displaces [³H]-MLA (KF=9.98 nM) and [¹²⁵I]-α-bungarotoxin (KF=4.33 nM). It is approximately 300-fold more potent than the natural agonist ACh (KF=3 μM). Encenicline inhibits the 5-HT₃ receptor by 51% at 10 nM, the lowest concentration tested. It shows selectivity for α7 nAChRs and does not activate or inhibit heteromeric α4β2 nAChRs. |
| 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].
In vivo, encenicline has good brain penetration and an adequate exposure time. At 0.3 mg/kg (p.o.), it significantly restores memory function in scopolamine-treated rats in an object recognition task (ORT). In a natural forgetting test, encenicline improved memory at 0.3 mg/kg (p.o.), an effect blocked by the selective α7 nAChR antagonist methyllycaconitine. Pharmacokinetic studies show that after a 0.4 mg/kg (i.p.) dose, it reaches peak brain concentration 2 hours post-administration and remains at effective concentrations for at least 4 hours. |
| Enzyme Assay |
Non-cellular assays for encenicline involve radioligand binding displacement studies to assess its affinity for the α7 nAChR. Membrane preparations from cells expressing the human α7 nAChR are incubated with a radiolabeled antagonist, such as [³H]-methyllycaconitine (MLA) or [¹²⁵I]-α-bungarotoxin, and varying concentrations of encenicline. After incubation and filtration, the bound radioactivity is measured, and IC₅₀ values are determined from displacement curves.
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| Cell Assay |
In vitro cellular assays for encenicline involve treating cells expressing the α7 nAChR with the compound and measuring receptor-mediated signaling. Functional assays, such as calcium influx assays, are used to measure the activation of the receptor. Cells are loaded with a calcium-sensitive dye and stimulated with encenicline. The increase in intracellular calcium is measured, and the EC₅₀ for receptor activation is determined. The compound's selectivity for α7 over other nAChR subtypes, such as α4β2, can be confirmed in parallel assays.
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| Animal Protocol |
In vivo animal experiments with encenicline are conducted in rodent models of cognitive impairment. Scopolamine-treated rats are used to model memory deficits, and encenicline is administered orally (0.3 mg/kg) to assess its ability to restore memory function in an object recognition task (ORT). A natural forgetting test with a 24-hour retention time is also used. The involvement of α7 nAChR is confirmed by co-administration of the selective antagonist methyllycaconitine, which blocks the effect.
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| ADME/Pharmacokinetics |
Encenicline has a molecular weight of 320.84 and a molecular formula of C₁₆H₁₇ClN₂OS. It is a solid powder with a purity of ≥98%. The compound is soluble in DMSO. It is typically stored at -20°C, protected from light and moisture. Encenicline demonstrates good brain penetration and binds moderately to rat plasma proteins with a mean fu of 0.11±0.01 (11%).
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| Toxicity/Toxicokinetics |
Encenicline is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. As an α7 nAChR agonist, it may cause side effects related to cholinergic activation, such as gastrointestinal disturbances. The compound has been investigated for cardiac repolarization effects. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
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| Additional Infomation |
Ensenicline has been investigated for the treatment of cognitive impairment, schizophrenia, Alzheimer's disease, cardiac repolarization, and central nervous system disorders.
Mechanism of Action Ensenicline is a selective, orally effective α7 nicotinic acetylcholine receptor agonist (α7 NAchR agonist). The mechanism of action of ensenicline may be similar to that of GTS-21. Auditory gating is a biological indicator that measures the ability to suppress an evoked response to the second of two auditory stimuli; auditory gating is impaired in patients with schizophrenia. Sensory gating deficits are associated with attention deficits and may lead to cognitive symptoms and perceptual disturbances. This inhibitory process involves the release of γ-aminobutyric acid (GABA) from hippocampal interneurons mediated by α(7) nicotinic receptors, representing a potential new target for therapeutic interventions in schizophrenia. Encenicline (EVP-6124; CAS 550999-75-2) is a novel, selective, and orally active α7 nAChR agonist. It displaces [³H]-MLA with a KF of 9.98 nM and is approximately 300-fold more potent than ACh. Encenicline has been investigated for the treatment of cognitive impairment in schizophrenia and Alzheimer's disease and has shown promising results in improving cognitive function and memory. |
| 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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