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Purity: ≥98%
SR17018 is an agonist of the μ-opioid-receptor (MOR) which binds to GTPγS with EC50 value of 97 nM. SR17018 demonstrates no discernible impact on triggering the recruitment of βarrestin2 to the MOR at concentrations lower than 10 μM. SR17018 facilitates signaling via G proteins or βarrestin2. G protein signaling bias extends the therapeutic window, permitting antinociception in the absence of respiratory suppression, whereas compounds biased toward βarrestin, like fentanyl, are more likely to cause respiratory suppression at low analgesic doses. There were greater variations in the compounds' capacity to cause βarrestin2 recruitment to the MOR. For example, SR-17018, did not show any noteworthy effectiveness in the βarrestin2 EFC assay until a concentration of 10 μM.
| Targets |
MOR ( EC50 = 97 nM )
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| Enzyme Assay |
A commercial enzyme fragment complementation assay (β-galactosidase) was utilized to ascertain the recruitment of βarrestin2 to the human MOR. Prior to measuring the signal, U2OS-βarrestin-hMOR PathHunter cells were plated in Assay Complete Cell Plating 5 Reagent (DiscoveRx) in a 384-well, white-walled assay microplate (Greiner Bio-One) at a density of 5,000 cells per well 16–20 hours earlier. βarrestin2 recruitment was assessed using the PathHunter Detection Kit with the β-galactosidase substrate to detect functional β-galactosidas after cells were treated for 90 minutes at 37°C with increasing concentrations of test compounds. A SpectraMax M5e Microplate Reader (Molecular Devices) was used to measure the increase in luminescence that resulted. For the PathHunter U2OS OPRM1 βarrestin cells, the average vehicle was 446 ± 25 RLU, while the average fold over vehicle for DAMGO was 36 ± 1.
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| Cell Assay |
The CHO-hMOR, -hDOR, and -hKOR cells were seeded at a density of 4,000 cells per well in Opti-MEM containing 1% FBS in a 384-well, white-walled, 30 μl-volume microplate (Greiner Bio-One) four hours before the assay. 20 μM forskolin, 25 μM 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro-20-1724), and escalating concentrations of test compounds were applied to the cells for 30 minutes at 25°C. Next, we used Cisbio's Homogeneous Time-Resolved Fluorescence resonance energy transfer (FRET) cAMP HiRange assay (Cisbio-62AM6PEC) to measure the inhibition of cAMP. At 620 and 665 nm, fluorescence was measured with a PerkinElmer Envision Multilabel Reader. The formula for calculating FRET was 665 nm / 620 nm. For CHO-hMOR cells, the average vehicle ratio was 3134 ± 99, while for DAMGO, the average fold over vehicle was 2.2 ± 0.04. For CHO-hDOR cells, the average vehicle ratio was 2962 ± 181, and for SNC80, the average fold over vehicle was 1.6 ± 0.04. For CHO-hKOR cells, the average vehicle ratio was 2965 ± 153, and for U69,593, the average fold over vehicle was 1.9 ± 0.12.
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| References |
| Molecular Formula |
C₁₉H₁₈CL₃N₃O
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| Molecular Weight |
410.72
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| Exact Mass |
409.05
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| Elemental Analysis |
C, 55.56; H, 4.42; Cl, 25.89; N, 10.23; O, 3.90
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| CAS # |
2134602-45-0
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| Appearance |
Solid powder
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| SMILES |
C1CN(CCC1N2C3=CC(=C(C=C3NC2=O)Cl)Cl)CC4=CC=C(C=C4)Cl
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| InChi Key |
LAGUDYUGRSQDKS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H18Cl3N3O/c20-13-3-1-12(2-4-13)11-24-7-5-14(6-8-24)25-18-10-16(22)15(21)9-17(18)23-19(25)26/h1-4,9-10,14H,5-8,11H2,(H,23,26)
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| Chemical Name |
5,6-dichloro-3-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-1H-benzimidazol-2-one
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.04 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 (3.04 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 | 2.4347 mL | 12.1737 mL | 24.3475 mL | |
| 5 mM | 0.4869 mL | 2.4347 mL | 4.8695 mL | |
| 10 mM | 0.2435 mL | 1.2174 mL | 2.4347 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.
Functional Effects of MOR Agonists at the Human DOR, KOR, and NOP. |
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SR Compounds Are Potent Activators of GTPγS Binding but Have Differential βARRESTIN2 Signaling Profiles at the Human MOR. |
GTPγS Binding at Mouse MOR Expressed in CHO Cells and Mouse Brainstem Compared to βArrestin2 Recruitment to Mouse MOR. |
SR Agonists Cross the Blood Brain Barrier and Are Present in Plasma 6 hr after Injection. |
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Agonists That Displayed G Protein-Signaling Bias in the Cell-Based Assays Promote Antincocicpetion with Less Respiratory Suppression. |
Dose Response for the Fentanyl, Morphine, and the SR Compounds in the Antinociception and Respiratory Assays and Efficacy in Female Mice. |
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