| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Encenicline targets the α7 nicotinic acetylcholine receptor (α7 nAChR), a ligand-gated ion channel that is widely expressed in the central nervous system and is involved in cognitive processes such as learning, memory, and attention. As a partial agonist, encenicline binds to the receptor and activates it, but with lower efficacy than a full agonist. By modulating α7 nAChR activity, encenicline enhances cholinergic neurotransmission and improves cognitive function.
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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 concentration tested, encenicline hydrochloride 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 (EVP-6124) did not inhibit or activate heteromeric α4β2 nAChR in binding or functional tests, however it did demonstrate selectivity for α7 nAChR[1].
In vitro, encenicline activates the α7 nAChR at low nanomolar concentrations in the brain. It potentiates the acetylcholine response of α7 nicotinic acetylcholine receptors, leading to enhanced cholinergic signaling. The compound's partial agonist activity at the α7 nAChR makes it a valuable tool for studying the role of this receptor in cognition and neurological disorders. |
| ln Vivo |
Ensenilin hydrochloride has an adequate exposure period and strong brain penetration. When rats treated with scopolamine (0.1 mg/kg, ip) were given encenicline hydrochloride (0.3 mg/kg, po), their memory function was greatly restored during the object recognition test (ORT). On this test, memory was not improved by donepezil (0.1 mg/kg) or ensenicline hydrochloride (0.03 mg/kg), however memory was entirely recovered when these sub-effective dosages were coadministered. The spontaneous forgetting test (ORT) demonstrated a 24-hour retention period. The administration of Encenicline hydrochloride (0.3 mg/kg) po resulted in an improvement in memory. Methylaconitine (0.3 mg/kg, ip or 10 μg, icv), a specific α7 nAChR antagonist, prevented this improvement. ..Rat plasma proteins exhibited a moderate binding of encenicline hydrochloride, with a mean fu of 0.11±0.01 (mean±SD), or 11%. Throughout the oral dosage range of 0.1–30 mg/kg, escenicline hydrochloride shows proportionate dose escalation. 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]. Encenicline hydrochloride (0.4 mg/kg, intraperitoneal injection) reaches peak brain concentrations two hours after delivery and maintains effective concentrations for at least four hours, according to pharmacokinetic studies. Without producing extended wakefulness or increased locomotor activity, encenicline hydrochloride administered to WT mice at ZT0 (0.4 mg/kg ip single dose) significantly elevated the saturation index of NMDAR in slices retrieved 4 hours later [ 2].
In vivo, encenicline has been shown to improve memory performance in rats. It has been studied in clinical trials for the treatment of cognitive impairments associated with schizophrenia and Alzheimer's disease. However, the development of encenicline was discontinued due to gastrointestinal adverse events observed in clinical trials. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for encenicline typically involve evaluating its binding affinity to the α7 nAChR using radioligand binding assays. The compound is incubated with membranes expressing the α7 nAChR and a radiolabeled ligand. The displacement of the radiolabeled ligand is measured, and the Ki is determined. Functional activity is assessed using calcium flux or electrophysiological assays to measure receptor activation.
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| Cell Assay |
For in vitro cell-based assays, encenicline is dissolved in DMSO and applied to cultured cells expressing the α7 nAChR at concentrations ranging from 1 nM to 10 µM. The effect on receptor activation is assessed by measuring calcium influx or other downstream signaling events. The compound's ability to potentiate acetylcholine responses is also evaluated.
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| Animal Protocol |
In vivo animal studies for encenicline are typically conducted in rodent models of cognitive impairment. The compound is administered orally or intraperitoneally at doses ranging from 0.1-10 mg/kg. Cognitive function is evaluated using behavioral tests such as the Morris water maze, novel object recognition, or attentional set-shifting tasks.
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| ADME/Pharmacokinetics |
Encenicline HCl has a molecular formula of C₁₆H₁₈Cl₂N₂OS and a molecular weight of 357.29 g/mol. It is a white to light yellow powder that is stored at room temperature in a cool and dark place under inert gas. The compound is air-sensitive and hygroscopic. It is supplied with a purity of >98.0% (HPLC).
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| Toxicity/Toxicokinetics |
Encenicline HCl is considered to have a manageable toxicity profile, but its development was discontinued due to gastrointestinal adverse events observed in clinical trials. Common side effects may include nausea, vomiting, and diarrhea. No significant hepatotoxicity or nephrotoxicity has been reported.
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| References |
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| Additional Infomation |
Encenicline HCl is a selective α7 nicotinic acetylcholine receptor partial agonist that was being developed for the treatment of cognitive impairments associated with schizophrenia and Alzheimer's disease. It is also known as EVP-6124 or MT-4666. Encenicline is not approved for clinical use and is intended for research purposes only. It is supplied by various research chemical suppliers for non-human use.
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| Molecular Formula |
C16H18CL2N2OS
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| Molecular Weight |
357.2979
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| Exact Mass |
356.051
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| CAS # |
550999-74-1
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| Related CAS # |
Encenicline;550999-75-2
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| PubChem CID |
46208542
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| Appearance |
White to off-white solid powder
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| LogP |
4.509
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
22
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| Complexity |
413
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1CN2CCC1[C@H](C2)NC(=O)C3=CC4=C(S3)C(=CC=C4)Cl.Cl
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| InChi Key |
OIJYTJGIDVTCFF-ZOWNYOTGSA-N
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| InChi Code |
InChI=1S/C16H17ClN2OS.ClH/c17-12-3-1-2-11-8-14(21-15(11)12)16(20)18-13-9-19-6-4-10(13)5-7-19/h1-3,8,10,13H,4-7,9H2,(H,18,20)1H/t13-/m0./s1
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| Chemical Name |
(R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride.
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| Synonyms |
EVP-6124 HCl EVP 6124 EVP6124 MT-4666 MT4666 MT 4666 Encenicline HCl.
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~139.94 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.00 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 25.0 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: ≥ 2.5 mg/mL (7.00 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 25.0 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: ≥ 2.5 mg/mL (7.00 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 | 2.7988 mL | 13.9938 mL | 27.9877 mL | |
| 5 mM | 0.5598 mL | 2.7988 mL | 5.5975 mL | |
| 10 mM | 0.2799 mL | 1.3994 mL | 2.7988 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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