| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Histamine H3 receptor (H3R).
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|---|---|
| ln Vitro |
The samelisant free base has very high selectivity for H3R and inverse agonist action. Treatment with 1, 10, and 100 nM of Samelisant increases the pEC50 value of histamine (8.5) for the human H3 receptor to 8.2, 7.3, and 6.2, respectively. The rat H3 receptor's pEC50 value for histamine (8.2) rises to 7.9, 7.4, and 6.4 following exposure to 1, 10, and 100 nmol/L of Samelisant, respectively[1]. According to the pA2 values for rat H3R and human H3R, the samelisant free base binds to the orthosteric site in a reversible manner with Kb values of 1.1 nM and 1.3 nM, respectively[1]. While samelisant free base had no effect on dopamine levels in the striatum or nucleus accumbens, it does modify dopamine and norepinephrine levels in the cerebral cortex [1].
Samelisant is a potent and selective H3 receptor inverse agonist with Ki values of 8.7 nM for the human H3 receptor and 9.8 nM for the rat H3 receptor. It exhibits good brain penetration and oral bioavailability. As an inverse agonist, it reduces the constitutive activity of the H3 receptor. |
| ln Vivo |
When orexin mutant mice undergo treatment with Samelisant (10 and 30 mg/kg, po) free base, their sleep electroencephalography (EEG) results show a considerable increase in wakefulness and a corresponding decrease in non-rapid eye movement sleep (NREM) sleep[1]. In an animal model related to narcolepsy, samelisant free base also significantly reduces direct rapid eye movement (REM) sleep onset (DREM) episodes[1]. This indicates that samelisant free base has anticataplectic effects. In mice treated with samelisant free base, tele-methylhistamine levels rise in a dose-dependent manner, signifying the activation of histaminergic neurotransmission[1].
In vivo, samelisant has been investigated for the potential treatment of narcolepsy and other sleep-related disorders. As an H3 receptor inverse agonist, it modulates the histaminergic system and may improve wakefulness and cognitive function. |
| Enzyme Assay |
In vitro receptor binding assays for samelisant are performed to evaluate its affinity for the H3 receptor. Radioligand binding studies using membrane preparations from cells expressing human or rat H3 receptors are conducted. The compound's ability to displace a specific radiolabeled H3 ligand is measured to calculate its Ki values.
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| Cell Assay |
In vitro cell-based assays are conducted using cells expressing the human or rat H3 receptor. The cells are treated with samelisant, and inverse agonist activity is measured by assessing its ability to reduce constitutive H3 receptor activity, such as the inhibition of cAMP accumulation.
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| Animal Protocol |
Animal/Disease Models: Male Wistar rats or male C57BL6J mice[1]
Doses: 1, 3, 10, and 30 mg/kg Route of Administration: Oral administration Experimental Results: Produced a dose-dependent increase in t-MH levels in the frontal cortex, hypothalamus and cerebrospinal fluid (CSF) of male Wistar rats. Produced a significant increase in t-MH levels of the frontal cortex, striatum and hypothalamus in mice. In vivo animal studies are conducted in rodent models to evaluate the effects of samelisant on sleep-wake cycles and narcolepsy. The compound is typically administered orally, and its effects on wakefulness, sleep architecture, and cataplexy are assessed. |
| ADME/Pharmacokinetics |
Samelisant is an orally bioavailable compound with good brain penetration. Detailed pharmacokinetic parameters such as half-life, volume of distribution, and clearance are not extensively documented in publicly available literature.
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| Toxicity/Toxicokinetics |
No specific toxicity data are publicly available for samelisant. As an H3 receptor inverse agonist, its toxicity profile is expected to be related to its mechanism of action. Standard safety precautions should be followed when handling this compound.
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| References | |
| Additional Infomation |
SUVN-G3031 is being investigated in the clinical trial NCT02342041 (a study investigating the safety, tolerability and pharmacokinetics of SUVN-G3031 in healthy subjects).
Samelisant free base (SUVN-G3031 free base) is a potent and selective H3 receptor inverse agonist with Ki values of 8.7 nM (human) and 9.8 nM (rat). It has been investigated for the potential treatment of narcolepsy and other sleep-related disorders. The compound is not approved for human therapeutic use and is strictly for research purposes. |
| Molecular Formula |
C21H31N3O3
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|---|---|
| Molecular Weight |
373.49
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| Exact Mass |
373.236
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| CAS # |
1394808-82-2
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| Related CAS # |
Samelisant;1394808-20-8
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| PubChem CID |
60151477
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| Appearance |
Typically exists as solid at room temperature
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
562.4±50.0 °C at 760 mmHg
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| Flash Point |
294.0±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.597
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| LogP |
2.56
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
463
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C1C=CC(=CC=1)NC(CN1CCOCC1)=O)C1CCN(CC1)C1CCC1
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| InChi Key |
LNXDUSQEXVQFGP-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H31N3O3/c25-21(16-23-12-14-26-15-13-23)22-17-4-6-19(7-5-17)27-20-8-10-24(11-9-20)18-2-1-3-18/h4-7,18,20H,1-3,8-16H2,(H,22,25)
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| Chemical Name |
N-[4-(1-cyclobutylpiperidin-4-yl)oxyphenyl]-2-morpholin-4-ylacetamide
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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 | 2.6774 mL | 13.3872 mL | 26.7745 mL | |
| 5 mM | 0.5355 mL | 2.6774 mL | 5.3549 mL | |
| 10 mM | 0.2677 mL | 1.3387 mL | 2.6774 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.
Link: https://clinicaltrials.gov/ct2/show/NCT07540364
Conditions:NarcolepsyLink: https://clinicaltrials.gov/ct2/show/NCT04072380
Conditions:NarcolepsyLink: https://clinicaltrials.gov/ct2/show/NCT05530447
Conditions:Narcolepsy
Title:A Study to Investigate the Effect of Food, Gender, and Age on the Pharmacokinetic Profile of SUVN-G3031 in Healthy Subjects
Status:Completed
updateDate:2017-09-25
Ctid:NCT02881294
Link: https://clinicaltrials.gov/ct2/show/NCT02881294
Conditions:Cognitive DisordersLink: https://clinicaltrials.gov/ct2/show/NCT02342041
Conditions:Cognitive DisordersProducts are for research use only; We do not sell to patients
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