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SR17018
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SR17018图片
CAS NO:2134602-45-0
规格:≥98%
包装与价格:
包装价格(元)
1mg电议
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW) 410.72
Formula C19H18Cl3N3O
CAS No. 2134602-45-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 6 mg/mL
Water:
Ethanol:
Chemical Name
SynonymsSR17018; SR-17018; SR 17018
SMILES Code O=C1NC2=CC(Cl)=C(Cl)C=C2N1C3CCN(CC4=CC=C(Cl)C=C4)CC3
实验参考方法
In Vitro

In vitro activity: SR17018 is a μ-opioid-receptor (MOR) agonist, binding with GTPγS, with an EC50 of 97 nM. SR17018 shows no obvious effect on inducing βarrestin2 recruitment to the MOR at below 10 μM. SR17018 promotes signaling through G proteins or βarrestin2.


Kinase Assay: To determine βarrestin2 recruitment to the human MOR a commercial enzyme fragment complementation assay (β-galactosidase) was used. U2OS-βarrestin-hMOR PathHunter cells were plated at a density of 5,000 cells per well of a 384-well, white-walled assay microplate (Greiner Bio-One) in Assay Complete Cell Plating 5 Reagent (DiscoveRx) 16-20 hr prior to measuring the signal. Cells were treated for 90 min with increasing concentrations of test compounds at 37°C and βarrestin2 recruitment was determined using the PathHunter Detection Kit with the β-galactosidase substrate to detect functional β-galactosidas. The resulting increase in luminescence was measured using a SpectraMax M5e Microplate Reader (Molecular Devices). The average vehicle for the PathHunter U2OS OPRM1 βarrestin cells was 446 ± 25 RLU and the average fold over vehicle for DAMGO was 36 ± 1.


Cell Assay: CHO-hMOR, -hDOR and -hKOR cells were plated at a density of 4,000 cells per well of a 384-well, white-walled, 30 μl-volume microplate (Greiner Bio-One) in Opti-MEM containing 1% FBS 4 hr prior to assaying. Cells were treated with 20 μM forskolin, 25 μM 4-(3-Butoxy-4-methoxybenzyl)imidazolidin-2-one (Ro-20-1724) and increasing concentrations of test compounds for 30 min at 25°C. Inhibition of cAMP was then determined using the Homogeneous Time-Resolved Fluorescence resonance energy transfer (FRET) cAMP HiRange assay by Cisbio (Cisbio-62AM6PEC). Fluorescence was measured at 620 and 665 nm using an Envision Multilabel Reader (PerkinElmer). FRET was calculated by the ratio of 665 nm / 620 nm. The average vehicle ratio for CHO-hMOR cells was 3134 ± 99 and the average fold over vehicle for DAMGO was 2.2 ± 0.04. The average vehicle ratio for CHO-hDOR cells was 2962 ± 181 and the average fold over vehicle for SNC80 was 1.6 ± 0.04. The average vehicle ratio for CHO-hKOR cells was 2965 ± 153 and the average fold over vehicle for U69,593 was 1.9 ± 0.12.

In VivoPharmacokinetic parameters were determined in the C57BL/6J mice by i.p. dosing. Plasma was generated by standard centrifugation techniques, resulting in ~10 μL of plasma that was immediately frozen. For brain collection, mice were sacrificed by cervical dislocation and brains were isolated and flash frozen in liquid nitrogen. Drug levels were determined using a LC (Shimadzu)-tandem mass spectrometry (AB Sciex) operated in positive-ion mode using multiple reaction monitoring methods (Brust et al., 2016). Plasma protein binding for fentanyl and morphine was determined using Rapid Equilibrium Dialysis (RED) devices (ThermoFisher). For the SR compounds, plasma samples (0.5 mL at 0.5 μM test compound) were prepared and 900 μL was transferred to a 2 mL polycarbonate ultracentrifuge tube. The sample was centrifuged at 400,000 x g for two hr using a Beckman Coulter Optima Max ultracentrifuge (130,000 RPM max) with a TLA 120.2 rotor held at 25°C. The centrifuged sample separates into three layers. The protein-rich bottom layer contains most of the albumin and is easily visualized. The top layer is not as easily discerned, but contains a high concentration of lipoproteins. The middle layer (1-2 mm below surface using the described conditions) has very low protein concentrations and can be used to determine the amount of unbound drug. The percent unbound compound was determined by LC-MS/MS by comparison of the compound concentration in the middle layer of the centrifuged sample to the concentration of a parallel sample that did not undergo centrifugation.
Animal modelC57BL/6J mice
Formulation & Dosage i.p.
References Cell. 2017 Nov 16;171(5):1165-1175.e13.