Samelisant (SUVN-G3031) free base is an orally bioavailable, BBB (blood-brain barrier)-passing, selective histamine H3 receptor (H3R) inverse agonist. Samelisant free base has similar binding affinities for human (hH3R; Ki=8.7 nM) and rat (rH3R; Ki=9.8 nM) H3R, indicating no interspecies differences. Samelisant free base may be utilized to study sleep-related disorders.

Physicochemical Properties

Molecular Formula	C21H31N3O3
Molecular Weight	373.49
Exact Mass	373.236
CAS #	1394808-82-2
Related CAS #	Samelisant;1394808-20-8
PubChem CID	60151477
Appearance	Typically exists as solid at room temperature
Density	1.2±0.1 g/cm3
Boiling Point	562.4±50.0 °C at 760 mmHg
Flash Point	294.0±30.1 °C
Vapour Pressure	0.0±1.5 mmHg at 25°C
Index of Refraction	1.597
LogP	2.56
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	5
Rotatable Bond Count	6
Heavy Atom Count	27
Complexity	463
Defined Atom Stereocenter Count	0
SMILES	O(C1C=CC(=CC=1)NC(CN1CCOCC1)=O)C1CCN(CC1)C1CCC1
InChi Key	LNXDUSQEXVQFGP-UHFFFAOYSA-N
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)
Chemical Name	N-[4-(1-cyclobutylpiperidin-4-yl)oxyphenyl]-2-morpholin-4-ylacetamide
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].
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].
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.
References	[1]. Samelisant (SUVN-G3031), a potent, selective and orally active histamine H3 receptor inverse agonist for the potential treatment of narcolepsy: pharmacological and neurochemical characterisation. Psychopharmacology (Berl). 2021 Jun;238(6).
Additional Infomation	SUVN-G3031 is under investigation in clinical trial NCT02342041 (A Study to Investigate the Safety, Tolerability and Pharmacokinetics of SUVN-G3031 in Healthy Subjects).

Solubility Data

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

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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (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.