Cebranopadol-GRT6005-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECebranopadolCat. No.: HY-15536CAS No.: 863513-91-1Synonyms: GRT6005分式: CHFNO分量: 378.48作靶点: Opioid Receptor作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMS

2、O : 6.67 mg/mL (17.62 mM; Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 0.67 mg/mL (1.77 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 0.67 mg/mL (1.77 mM); Suspended solution; Need ultrasonic1/3 Master of Small Molecules 您边

3、的抑制剂师www.MedChemE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 0.67 mg/mL (1.77 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 CebranopadolNOP 和 opioid receptor 激动剂，作于NOP，MOP，KOP 和-阿肽(DOP)受体，Ki/EC50 分别为 0.9 nM/13 nM，0.7 nM/1.2 nM，2.6 nM/17 nM，18 nM/110 nM。IC50 & Target EC50: 132 nM (hNOP receptor), 1.20

4、.4 nM (hMOP receptor), 175 nM (hKOP receptor), 11028 nM(hDOP receptor) 1体外研究 Cebranopadol binds with high affinity (subnanomolar to nanomolar range) to nociceptin/orphanin FQ peptide(NOP) and opioid receptors, with Ki of 10.5 nM, 2.41.2 nM, and 6411 nM for rat NOP, mu-opioid peptide(MOP) receptor, a

5、nd kappa-opioid peptide (KOP) receptor, and with Ki of 0.90.2 nM, 0.70.3 nM, and2.61.4 nM for Rat NOP, MOP, and KOP receptor 1.体内研究 Cebranopadol exhibits highly potent and efficacious antinociceptive and antihypersensitive effects in severalrat models of acute and chronic pain (tail-flick, rheumatoi

6、d arthritis, bone cancer, spinal nerve ligation,diabetic neuropathy) with ED50 values of 0.5-5.6 g/kg after intravenous and 25.1 g/kg after oraladministration. In comparison with selective MOP receptor agonists, cebranopadol is more potent in modelsof chronic neuropathic than acute nociceptive pain.

7、 Cebranopadols duration of action is long (up to 7 hoursafter intravenous 12 g/kg; 9 hours after oral 55 g/kg in the rat tail-flick test). The antihypersensitive activityof cebranopadol in the spinal nerve ligation model is partially reversed by pretreatment with the selectiveNOP receptor antagonist

8、 J-113397 or the opioid receptor antagonist naloxone, indicating that both NOP andopioid receptor agonism are involved in this activity. Development of analgesic tolerance in the chronicconstriction injury model is clearly delayed compared with that from an equianalgesic dose of morphine(complete to

9、lerance on day 26 versus day 11, respectively). Unlike morphine, cebranopadol did not disruptmotor coordination and respiration at doses within and exceeding the analgesic dose range. Cebranopadol,by its combination of agonism at NOP and opioid receptors, affords highly potent and efficacious analge

10、sia invarious pain models with a favorable side effect profile 1.PROTOCOLKinase Assay 1 Human MOP, DOP, KOP, and NOP receptor binding assays are run in microtiter plates with wheat germagglutinin-coated scintillation proximity assay beads. N-allyl-2,3-3Hnaloxone and tyrosyl-3,5-3HdeltorphinII, 3HCi-

11、977, and leucyl-3Hnociceptin are used as ligands for the MOP, DOP, KOP, and NOP receptorbinding studies, respectively. The KD values of the radioligands used for the calculation of Ki values areprovided as supplemental information. The assay buffer used for the MOP, DOP, and KOP receptor bindingstud

12、ies is 50 mM Tris-HCl (pH 7.4) supplemented with 0.052 mg/mL bovine serum albumin. For the NOPreceptor binding studies, the assay buffer used is 50 mM HEPES, 10 mM MgCl2, 1 mM EDTA (pH 7.4). Thefinal assay volume of 250 L/well included 1 nM 3Hnaloxone, 1 nM 3Hdeltorphin II, 1 nM 3HCi-977, or0.5 nM 3

13、Hnociceptin as a ligand and cebranopadol in dilution series. Cebranopadol is diluted with 25%2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEDMSO in water to yield a final 0.5% DMSO concentration, which also served as a respective vehicle control.Assays are started by the addition of beads (1 mg be

14、ads/well), which had been preloaded for 15 minutes atroom temperature with 23.4 g of human MOP membranes, 12.5 g of human DOP membrane, 45 g ofhuman KOP membranes, or 25.4 g of human NOP membranes per 250 L of final assay volume. Aftershort mixing, the assays are run for 90 minutes at room temperatu

15、re. The microtiter plates are thencentrifuged for 20 minutes at 500 rpm, and the signal rate is measured by means of a 1450 MicroBeta Trilux.IC50 values reflecting 50% displacement of 3Hnaloxone-, 3Hdeltorphin II-, 3HCi-977-, or 3Hnociceptin-specific receptor binding are calculated by nonlinear regr

16、ession analysis. Individual experiments are run induplicate and are repeated three times in independent experiments 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Rats 1Administration 1 The pharmacokinetic properties of cebranopadol in rats ar

17、e investigated after a single intravenous dose of160 g/kg cebranopadol. The intravenous dose is administered as a bolus in a volume of 2 mL/kg with acatheter in the vena femoralis. Blood samples (200 L/sample) are withdrawn via an implanted arterialcatheter (arteria carotis) by an automated blood sa

18、mpling system at the following sampling times: 0(predose), 5, 15, 30, 60, 180, 360, 720, and 1440 minutes after administration. Blood samples arecentrifuged, and plasma is separated. Plasma concentrations of cebranopadol are determined using avalidated liquid chromatography-tandem mass spectrometry

19、method. The lower limit of quantification forcebranopadol in this method is 0.05 ng/mL using a sample volume of 50 L of plasma.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Signal. 2019 Mar 26;12(574). pii: eaau8072. Inflammopharmacolo

20、gy. 2018 Apr;26(2):361-374. J Pharmacol Exp Ther. 2017 Sep;362(3):378-384. J Pharmacol Exp Ther. 2017 Aug;362(2):254-262.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Linz K, et al. Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agon