Vornorexant (ORN-0829; TS-142) is a potent dual OX1R and OX2R antagonist (inhibitor) with IC50s of 1.05 nM and 1.27 nM, respectively. Vornorexant has shown potent sleep-promoting effects in animal models and may be utilized to study insomnia.

Physicochemical Properties

Molecular Formula	C23H22FN7O2
Molecular Weight	447.464887142181
Exact Mass	447.181
CAS #	1517965-94-4
PubChem CID	137419776
Appearance	White to light yellow solid powder
LogP	2.5
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	5
Heavy Atom Count	33
Complexity	667
Defined Atom Stereocenter Count	1
SMILES	FC1=CN=C(C=C1)C1C=CN(C[C@H]2N(C(C3=CC(C)=CC=C3N3N=CC=N3)=O)CCCO2)N=1
InChi Key	AEZZJXJIJFSUEM-QFIPXVFZSA-N
InChi Code	InChI=1S/C23H22FN7O2/c1-16-3-6-21(31-26-8-9-27-31)18(13-16)23(32)30-10-2-12-33-22(30)15-29-11-7-20(28-29)19-5-4-17(24)14-25-19/h3-9,11,13-14,22H,2,10,12,15H2,1H3/t22-/m0/s1
Chemical Name	[(2S)-2-[[3-(5-fluoropyridin-2-yl)pyrazol-1-yl]methyl]-1,3-oxazinan-3-yl]-[5-methyl-2-(triazol-2-yl)phenyl]methanone
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

Targets	OX2 Receptor
ln Vivo	At a po, vornorexant (oral dosage; 1–10 mg/kg) shows strong sleep-promoting properties. in a rat polysomnogram study at a dosage of 1 mg/kg. The proportion of total sleep increases in a dose-dependent manner as a result[1]. In rats and dogs, vornorexant has ideal PK characteristics, including a quick Tmax and brief half-lives. In rats and dogs, the T1/2 is 0.238 hours and 1.16 hours, respectively[1].
Animal Protocol	Animal/Disease Models: Rat[1] Doses: 1, 3, 10 mg/kg Route of Administration: Oral administration to rats prior to turning the light off (start of the active phase); 1-10 mg/kg Experimental Results: Possessed promising sleep-inducing and sleep-promoting effects.
References	[1]. Discovery of ORN0829, a potent dual orexin 1/2 receptor antagonist for the treatment of insomnia. Bioorg Med Chem. 2020 Jul 1;28(13):115489.

Solubility Data

Solubility (In Vitro)

DMSO: ≥ 100 mg/mL (223.48 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 1.25 mg/mL (2.79 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 12.5 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: ≥ 1.25 mg/mL (2.79 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 12.5 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. Solubility in Formulation 3: ≥ 1.25 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.2348 mL	11.1742 mL	22.3484 mL
	5 mM	0.4470 mL	2.2348 mL	4.4697 mL
	10 mM	0.2235 mL	1.1174 mL	2.2348 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.