LY-2940094 is a novel, potent, selective and orally bioavailable nociceptin receptor (NOP receptor) antagonist that can be potentially used for the treatment of major depressive disorder and alcoholism. It possesses strong antagonist potency (Kb=0.166 nM) and affinity (Ki=0.105 nM). In animal models, ethanol self-administration is decreased by LY-2940094.
Physicochemical Properties
| Molecular Formula | C22H23CLF2N4O2S |
| Molecular Weight | 480.958429574966 |
| Exact Mass | 480.12 |
| Elemental Analysis | C, 54.94; H, 4.82; Cl, 7.37; F, 7.90; N, 11.65; O, 6.65; S, 6.67 |
| CAS # | 1307245-86-8 |
| Related CAS # | LY2940094 tartrate; 1307245-87-9 |
| PubChem CID | 52914971 |
| Appearance | White to yellow solid powder |
| LogP | 3.1 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 32 |
| Complexity | 672 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | NKQHBJNRBKHUQR-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H23ClF2N4O2S/c1-14-16(11-29(27-14)20-15(12-30)3-2-6-26-20)10-28-7-4-21(5-8-28)19-17(9-18(23)32-19)22(24,25)13-31-21/h2-3,6,9,11,30H,4-5,7-8,10,12-13H2,1H3 |
| Chemical Name | [2-[4-[(2-chloro-4,4-difluorospiro[5H-thieno[2,3-c]pyran-7,4'-piperidine]-1'-yl)methyl]-3-methylpyrazol-1-yl]pyridin-3-yl]methanol |
| Synonyms | BTRX 246040; BTRX246040; BTRX-246040; LY-2940094; LY 2940094; LY2940094 |
| 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 | NOP Receptor/ORL1 |
| ln Vivo | LY2940094 (3, 10, or 30 mg/kg; 2-3 mL/kg; side wall daily; for 4 days) Drinking sites reduce alcohol preference in Indiana (P) and Malkigian Sardinia (msP) in large animals Model: Female alcoholic (P) rat (250-320 g); rat, does not affect food/water recognition or locomotor activity [1]. Male Malchigian Sardinian alcohol-preferring (msP) rats (400-450 g) [1] Dosage: 3, 10, or 30 mg/kg; 2-3 mL/kg Administration: Oral; daily; 4-day results: Reduced home cage ethanol self-administration. |
| Animal Protocol |
Female Alcohol-Preferring (P) rats (250-320 g); Male Marchigian Sardinian Alcohol-Preferring (msP) rats (400-450 g) 3, 10, or 30 mg/kg; 2-3 mL/kg Administered orally; daily; 4 days |
| References |
[1]. A Novel, Orally Bioavailable Nociceptin Receptor Antagonist, LY2940094, Reduces Ethanol Self-Administration and Ethanol Seeking in Animal Models. Alcohol Clin Exp Res. 2016 May;40(5):945-54. |
| Additional Infomation | BTRX-246040 is under investigation in clinical trial NCT03193398 (BTRX-246040 Administered Once Daily to Patients With Major Depressive Disorder). |
Solubility Data
| Solubility (In Vitro) | DMSO: ~41.7 mg/mL (~86.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.32 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 20.8 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: ≥ 2.08 mg/mL (4.32 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 20.8 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: ≥ 2.08 mg/mL (4.32 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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 | 2.0792 mL | 10.3959 mL | 20.7917 mL | |
| 5 mM | 0.4158 mL | 2.0792 mL | 4.1583 mL | |
| 10 mM | 0.2079 mL | 1.0396 mL | 2.0792 mL |