Oliceridine-hydrochloride-TRV130-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEOliceridine hydrochlorideCat. No.: HY-16655ACAS No.: 1401031-39-7Synonyms: TRV130 (hydrochloride)分式: CHClNOS分量: 423.01作靶点: Opioid Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: 4C, stored under nitrogen* In solvent : -80C,

2、6 months; -20C, 1 month (stored undernitrogen)溶解性数据体外实验 DMSO : 38 mg/mL (89.83 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.3640 mL 11.8201 mL 23.6401 mL5 mM 0.4728 mL 2.3640 mL 4.7280 mL10 mM 0.2364 mL 1.1820 mL 2.3640 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备

3、液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Oliceridine hydrochloride (TRV130 hydrochloride)是新颖的 MOR 激动剂，能够优先激活 G-protein 信号通路，对 -arrestin 的作稍弱。体外研究 Oliceridine (TRV130) elicits robust G protein signaling, with potency and efficacy similar to morphine, but withfar less -arrestin recruitment and receptor

4、 internalization 2.1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE体内研究 Oliceridine (TRV130) treatment produces robust antinociception, complete inhibition of gastrointestinalfunction, and weak abuse-related effects in mice 1. Oliceridine (TRV130) displays an ED50 of 0.9 mg/kg inan analgesic assay.

5、 Oliceridine analgesia is reversible in mice by administration of 3 mg/kg naloxone s.c. 15minutes after Oliceridine dosing. In the rat 52C hot plate, Oliceridine is 10-fold more potent than morphinewith ED50 of 0.32 and 3.2 mg/kg, respectively. Oliceridine (0.3 mg/kg, s.c.) possesses an improvedther

6、apeutic index of analgesia to constipation relative to morphine in mice 2. Oliceridine (TRV130; 1.2mg/kg, s.c.) significantly depresses respiration of mice 3.PROTOCOLKinase Assay 2 Equilibrium binding of unlabeled compounds is measured by inhibition of radioligand binding (3H-diperenorphine) to HEK

7、cell membranes expressing human MOR, KOR, and DOR. Unlabeled ligand andbuffer (50 mM Hepes, 5 mM MgCl2, 1 mM EGTA and 0.05% bovine serum albumin, pH 7.2, at 23C)containing radioligand are added to polypropylene 96-well plates. Assays are initiated by the addition ofmembrane (5-10 g protein/well) sus

8、pension. The concentration of 3H-diprenorphine (specific activity 50-52Ci/mmol), is 0.5-1 times the independently determined Kd. Compounds are diluted in DMSO and tested at afinal concentration of 1% DMSO. Nonspecific binding is defined in the presence of 1 M naloxone.Competition assays are performe

9、d at 23C for 3-4 hours to allow adequate time for equilibrium binding. In allassays, total radioligand bound to the filter is less than 10% of the total radioligand added. The separation ofbound from free radioligand is accomplished by rapid vacuum filtration of the incubation mixture over GF/Bfilte

10、r mats using a Brandel cell harvester. Filters are washed 2 times with 0.5 mL of ice-cold phosphatebuffered saline pH 7.0 containing 0.01% Triton 100. Radioactivity on the filters is quantified using aMicroBeta TriLux Liquid Scintillation Counter.MCE has not independently confirmed the accuracy of t

11、hese methods. They are for reference only.Animal Analgesia-like responses in are measured using a hotplate analgesia meter with dimensions of 29.2 26.7Administration 3 cm with mice restricted to a cylinder 8.9 cm in diameter and 15.2 cm high. Response is measured byrecording the latency to lick, flu

12、tter, or splay hind paw(s), or an attempt to jump out of the apparatus at 55 C,with a maximum cut-off time of 30 s. Once a response is observed or the cut-off time had elapsed, thesubject is immediately removed from the hotplate and placed back in its home cage. The animals areacclimated to the hotp

13、late, while cool, and a baseline analgesic response time is acquired several hoursbefore drug treatment and testing. Mice are injected with either vehicle (n=8), morphine (5 mg/kg, n=8 or 10mg/kg, n=8), Oliceridine (1.2 mg/kg, n=9) or PZM21 (10 mg/kg, n=8; 20 mg/kg, n=11; or 40 mg/kg, n=8).After inj

14、ection of drug, the analgesic effect expressed as percentage maximum possible effect (%MPE) ismeasured at 15, 30, 60, 90 and 120 min after drug treatment. If animals do not display hind paw lick, splay,or flutter, they are removed from the trial. Additionally, if animals attempt to jump out of the p

15、late or urinatedon the hotplate they are removed from the trial. To assess analgesia by the tail-flick assay, a tail-flickanalgesia meter. Mice are gently immobilized with a cotton towel and the tail base is placed on a radiant lightsource emitting a constant temperature of 56 C. The tail withdrawal

16、 latency is measured at similar timepoints as the hotplate assay after administration of vehicle (n=8), morphine (5 mg/kg, n=4; 10 mg/kg, n=8) orPZM21 (10 mg/kg, n=8; 20 mg/kg; n=14). The cut-off time for the heat source is set at 10 s to avoid tissuedamage. Analgesic response times are measured sim

17、ilar to the hotplate assayMCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEREFERENCES1. Altarifi AA, et al. Effects of acute and repeated treatment with the biased mu opioid receptor agonist TRV130 (olicer

18、idine) on measuresof antinociception, gastrointestinal function, and abuse liability in rodents. J Psychopharmacol. 2017 Jan 1:26988111662. DeWire SM, et al. A G protein-biased ligand at the -opioid receptor is potently analgesic with reduced gastrointestinal and respiratorydysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17.3. Manglik A, et al. Structure-based discovery of opio