LY2795050 is a novel, potent and selective κ-opioid Receptor (KOR) antagonist with an IC50 of 0.72 nM. It has the potential to be used as a PET tracer to image KOR in vivo.
Physicochemical Properties
| Molecular Formula | C23H22CLN3O2 |
| Molecular Weight | 407.893 |
| Exact Mass | 407.14 |
| Elemental Analysis | C, 67.73; H, 5.44; Cl, 8.69; N, 10.30; O, 7.84 |
| CAS # | 1346133-08-1 |
| Related CAS # | 1346133-08-1 |
| PubChem CID | 56851583 |
| Appearance | White to off-white solid powder |
| LogP | 5.601 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 29 |
| Complexity | 540 |
| Defined Atom Stereocenter Count | 1 |
| SMILES | O=C(N)C1=CC=C(OC2=CC=C(CN3[C@H](C4=CC=CN=C4)CCC3)C=C2)C(Cl)=C1 |
| InChi Key | LOOCZNLSXJHWTG-NRFANRHFSA-N |
| InChi Code | InChI=1S/C23H22ClN3O2/c24-20-13-17(23(25)28)7-10-22(20)29-19-8-5-16(6-9-19)15-27-12-2-4-21(27)18-3-1-11-26-14-18/h1,3,5-11,13-14,21H,2,4,12,15H2,(H2,25,28)/t21-/m0/s1 |
| Chemical Name | 3-chloro-4-[4-[[(2S)-2-pyridin-3-ylpyrrolidin-1-yl]methyl]phenoxy]benzamide |
| Synonyms | LY2795050; LY 2795050; LY-2795050; (S)-LY2795050 |
| 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 | KOR ( Ki = 0.72 nM ); KOR ( Kb = 0.63 nM ) |
| ln Vitro | LY2795050 exhibits antagonist activity with a Kb value of 0.63 nM and high affinity for the KOR with a Ki value of 0.72 nM[1]. |
| ln Vivo | LY2795050 (i.p., 0.032-0.1 mg/kg, 30 min) prevents dose-dependent grooming deficits caused by U50,488 in male and female mice[2]. Some behavioral effects of LY2795050 (i.p., 0.032-0.1 mg/kg, 0-150 min) exhibit sexual dimorphism[2]. |
| Animal Protocol |
C57BL/6J mice (gonadally intact, adult, male and female) 0.032-0.1 mg/kg i.p., 0.032-0.1mg/kg, 30 min |
| References |
[1]. Synthesis and evaluation of 11C-LY2795050 as a κ-opioid receptor antagonist radiotracer for PET imaging. J Nucl Med. [2]. Profile of a short-acting κ-antagonist, LY2795050, on self-grooming behaviors, forced swim test and locomotor activity: sex comparison in mice. J Psychopharmacol. 2021 May;35(5):579-590. |
Solubility Data
| Solubility (In Vitro) | DMSO: ~50 mg/mL (~122.6 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.13 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 25.0 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: ≥ 2.5 mg/mL (6.13 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 25.0 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: ≥ 2.5 mg/mL (6.13 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 25.0 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 | 2.4516 mL | 12.2582 mL | 24.5164 mL | |
| 5 mM | 0.4903 mL | 2.4516 mL | 4.9033 mL | |
| 10 mM | 0.2452 mL | 1.2258 mL | 2.4516 mL |