| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
EMD-386088 primarily targets the serotonin 6 receptor (5-HT6R), a G protein-coupled receptor (GPCR) that is predominantly expressed in the central nervous system, particularly in regions involved in cognition, learning, and memory, such as the hippocampus and cortex. It is a potent and selective 5-HT6R agonist with an EC50 of 1.0 nM. This high potency indicates that EMD-386088 binds with high affinity to the 5-HT6R and effectively activates it. The compound displays selectivity over other 5-HT receptors, with the exception of 5-HT3R, where it has an IC50 of 34 nM. This selectivity is important for minimizing off-target effects and for studying the specific role of 5-HT6R. Activation of 5-HT6R by EMD-386088 leads to the regulation of ERK1/2 activity. ERK1/2 is a key signaling pathway that regulates cell proliferation, differentiation, and survival. The compound's effects on ERK1/2 are mediated through both 5-HT6R-dependent and -independent mechanisms. EMD-386088 also induces cell death. The compound's potent and selective agonism of 5-HT6R makes it a valuable tool for studying the role of this receptor in cognitive function and neurological disorders.
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| ln Vitro |
Cell death is induced in a dose- and time-dependent manner by EMD386088 (1, 10, 60 μM; 0-18 hours) [1]. EMD386088 (1, 10, 60 μM) both 5-HT6R-dependently and 5-HT6R-independently affects ERK1/2 activity [1].
EMD-386088 demonstrates potent in vitro activity as a 5-HT6 receptor agonist. It has an EC50 of 1.0 nM for the 5-HT6 receptor, indicating exceptionally high potency. This means that it can activate the receptor at very low concentrations. EMD-386088 is inactive against other 5-HT receptors except 5-HT3R, where it has an IC50 of 34 nM. This selectivity is important for minimizing off-target effects and for studying the specific role of 5-HT6R. In cellular assays, EMD-386088 (1-60 μM) induces cell death in a dose- and time-dependent manner, indicating cytotoxic effects. It also regulates the activity of ERK1/2, a key signaling pathway, in both a 5-HT6R-dependent and -independent manner. This suggests that the compound's effects on cell signaling are complex and may involve multiple pathways. The compound's ability to induce cell death and modulate ERK1/2 activity suggests that it has potential applications in cancer research, in addition to its use in neuroscience. These in vitro findings establish EMD-386088 as a potent and selective 5-HT6R agonist with significant effects on cell viability and signaling. |
| ln Vivo |
In male Wistar rats, EMD386088 (1, 5, 10 mg/kg) reduced both long-term memory (LTM) and short-term memory (STM) at the 5 mg/kg dose but not at the 10 mg/kg level. impact [2]. The study found that EMD386088 (0, 2, 4 mg/kg) significantly reduced spontaneous alternation performance at the 2 mg/kg level. However, in C57BL/6J mice, the high dose of 4 mg/kg did not achieve statistical significance.
Specific in vivo activity data for EMD-386088 are not detailed in the provided references. However, given its potent and selective agonism of 5-HT6R, it is expected to have effects on cognitive function and behavior in animal models. 5-HT6R is known to be involved in learning, memory, and mood regulation, so EMD-386088 could be used to study these processes. The compound has the potential for the research of Alzheimer's disease (AD) and schizophrenia. In these diseases, dysfunction of serotonergic signaling is implicated. By activating 5-HT6R, EMD-386088 could modulate these pathways and potentially provide therapeutic benefits. Further in vivo studies are needed to fully characterize the pharmacological effects of EMD-386088 and to evaluate its potential therapeutic applications. |
| Enzyme Assay |
The in vitro enzyme/receptor binding (non-cellular) assay for EMD-386088 typically involves assessing its affinity for the 5-HT6 receptor and other serotonin receptors using radioligand binding techniques. In a typical protocol, membrane preparations from cells expressing the target receptor are incubated with a radiolabeled ligand (e.g., [3H]-LSD for 5-HT6R) and varying concentrations of EMD-386088. After incubation, the bound and free radioligand are separated by filtration or centrifugation, and the radioactivity is measured. The displacement of the radioligand by EMD-386088 is used to calculate its binding affinity (Ki or IC50). For EMD-386088, this method has been used to determine its EC50 of 1.0 nM for 5-HT6R and its IC50 of 34 nM for 5-HT3R. These binding studies are critical for characterizing the compound's affinity, selectivity, and binding kinetics at its molecular targets.
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| Cell Assay |
Cell viability assay [1]
Cell Types: HEK/HA-5-HT6R, native HEK293 Cell Tested Concentrations: 1, 10, 60 μM Incubation Duration: 0-18 hrs (hours) Experimental Results: Induced cells in HEK293 cells stably expressing HA-5-HT6R in dead (HEK/HA-5-HT6R) and native HEK293 cells in a dose- and time-dependent manner. Western Blot Analysis [1] Cell Types: HEK/HA-5-HT6R, native HEK293 Cell Tested Concentrations: 1, 10, 60 μM Incubation Duration: 0-18 h Experimental Results: 0-30 μM leads to ERK1/2 activation, in HEK/ In HA-5-HT6R cells, high doses of 60 μM delayed ERK1/2 activation. The in vitro cellular assay for EMD-386088 typically involves evaluating its effects on cell viability and signaling pathways. In a typical assay, cells (e.g., HEK293 cells expressing 5-HT6R) are treated with varying concentrations of EMD-386088 for a specified period. Cell viability is then measured using an MTT or similar assay to assess cytotoxicity. The results show that EMD-386088 (1-60 μM) induces cell death in a dose- and time-dependent manner. To study its effects on signaling, cells are treated with EMD-386088, and the phosphorylation of ERK1/2 is measured by Western blot using phospho-specific antibodies. The results show that EMD-386088 regulates ERK1/2 activity in both a 5-HT6R-dependent and -independent manner. These cellular assays are crucial for demonstrating the compound's functional activity in a relevant biological context. |
| Animal Protocol |
The in vivo animal experimental protocol for EMD-386088 would typically involve the use of rodent models to assess its effects on cognitive function and behavior. In a typical study, EMD-386088 would be administered to mice or rats, and its effects on learning and memory would be assessed using behavioral tests such as the Morris water maze or novel object recognition. The compound's effects on other behaviors, such as anxiety or depression, could also be evaluated. For studying its potential in schizophrenia, animal models of this disorder, such as the prepulse inhibition (PPI) test, could be used. While such studies are not detailed in the provided references, they would be essential for demonstrating the in vivo efficacy of EMD-386088.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic (PK) data for EMD-386088, such as half-life, clearance, volume of distribution, or bioavailability, are not reported in the available literature. However, the compound's potent activity and selectivity make it a promising candidate for further development. EMD-386088 has a molecular weight of 283.20 and is soluble in DMSO. Further studies are needed to fully characterize the PK properties of EMD-386088, including its absorption, distribution, metabolism, and excretion (ADME) profile.
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| Toxicity/Toxicokinetics |
Specific toxicity (toxicology) data for EMD-386088 are not reported in the available literature. However, the compound's ability to induce cell death in vitro suggests that it may have cytotoxic effects. The selectivity for 5-HT6R over other receptors may help to minimize off-target toxicity. Comprehensive toxicological assessments, including acute and chronic toxicity studies, genotoxicity, and carcinogenicity, would be necessary to fully evaluate the safety profile of EMD-386088 for potential therapeutic applications. The compound is for research use only.
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| References |
[1]. Yun HM, et al. 5-HT6 receptor ligands, EMD386088 and SB258585, differentially regulate 5-HT6 receptor-independent events. Toxicol In Vitro. 2011 Dec;25(8):2035-40.
[2]. Meneses A, et al. The effects of the 5-HT(6) receptor agonist EMD and the 5-HT(7) receptor agonist AS19 on memory formation. Behav Brain Res. 2008 Dec 16;195(1):112-9. [3]. Amodeo DA, et al. 5-HT6 receptor agonist EMD386088 impairs behavioral flexibility and working memory. Behav Brain Res. 2018 Sep 3;349:8-15. |
| Additional Infomation |
EMD-386088 is a potent and selective 5-HT6 receptor (5-HT6R) agonist with an EC50 of 1.0 nM. It is inactive against other 5-HT receptors except 5-HT3R (IC50 of 34 nM). EMD-386088 regulates ERK1/2 activity and induces cell death. It has the potential for the research of Alzheimer's disease (AD) and schizophrenia. The compound has a molecular formula of C14H16Cl2N2 and a molecular weight of 283.20. It is used as a pharmacological tool to study the role of 5-HT6 receptors in the central nervous system.
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| Molecular Formula |
C14H15CLN2
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| Molecular Weight |
246.74
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| Exact Mass |
282.069
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| CAS # |
1171123-46-8
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| Related CAS # |
54635-62-0;
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| PubChem CID |
56972198
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.637
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
18
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| Complexity |
315
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.ClC1=CC=C2C(C(=C(N2)C)C2CCNCC=2)=C1
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| InChi Key |
WWSNDUWIZDYGIQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H15ClN2.ClH/c1-9-14(10-4-6-16-7-5-10)12-8-11(15)2-3-13(12)17-9;/h2-4,8,16-17H,5-7H2,1H3;1H
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| Chemical Name |
5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole;hydrochloride
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| Synonyms |
EMD386088; EMD 386088; EMD-386088
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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 | 4.0528 mL | 20.2642 mL | 40.5285 mL | |
| 5 mM | 0.8106 mL | 4.0528 mL | 8.1057 mL | |
| 10 mM | 0.4053 mL | 2.0264 mL | 4.0528 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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