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2mg |
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5mg |
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10mg |
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25mg |
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50mg |
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Purity: ≥98%
Cebranopadol 1α,4α-stereoisomer is a stereoisomer of cebranopadol. Cebranopadol (also known as GRT-6005) is a brand-new, first-in-class drug that exhibits strong agonist activity on both the well-known mu opioid receptor and ORL-1 (an opioid receptor similar to -1). With ED50 values of 0.5-5.6 µg/kg after intravenous and 25.1 µg/kg after oral administration, cebranopadol is an analgesic nociceptin/orphanin FQ peptide (NOP) that shows high potency and efficacy in several rat models of acute and chronic pain (tail-flick, rheumatoid arthritis, bone cancer, spinal nerve ligation, diabetic neuropathy). Clinical Phase 2 and Phase 3 trials are evaluating it for the management of both acute and chronic pain. According to recent research, opioid and NOP receptor agonism combined may be a novel approach to treating cocaine addiction.
Targets |
NOP Receptor/ORL1
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ln Vitro |
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ln Vivo |
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Enzyme Assay |
In microtiter plates (Costar 3632; Corning Life Sciences, Tewksbury, MA), human MOP, DOP, KOP, and NOP receptor binding assays were conducted using wheat germ agglutinin-coated scintillation proximity assay beads (GE Healthcare, Chalfont St. Giles, UK). PerkinElmer Life and Analytical Sciences (Boston, MA) is the source of cell membrane preparations for Chinese hamster ovary K1 cells transfected with the human MOP receptor (Art.-No. RBHOMM, lot-No. 307-065-A) or the human DOP receptor (Art.-No. RBHODM, lot-No. 423-553-B), as well as human embryonic kidney cell line 293 cells transfected with the human NOP receptor (Art.-No. RBHORLM, lot-No. 1956) or the human KOP receptor (Art.-No. 6110558, lot-No. 295-769-A). The ligands for the MOP, DOP, KOP, and NOP receptor binding studies were [N-allyl-2,3-3H]naloxone, [tyrosyl-3,5-3H]deltorphin II, and [3H]Ci-977, which were acquired from PerkinElmer Life and Analytical Sciences, respectively. Leucyl-3H]nociceptin was obtained from GE Healthcare.
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Cell Assay |
Cebranopadol was tested for its agonistic activity on human recombinant MOP, DOP, or NOP receptor-expressing cell membranes from Chinese hamster ovary K1 cells, or KOP receptor-expressing cell membranes from human embryonic kidney cell line 293 cells. For each assay, 10 µg of membrane proteins was incubated for 45 minutes at 25°C with 0.4 nM [35S]GTPγS (GE Healthcare) and various concentrations of agonists in a buffer containing 20 mM HEPES (pH 7.4), 100 mM NaCl, 10 mM MgCl2, 1 mM EDTA, 1 mM dithiothreitol, 1.28 mM NaN3, and 10 µM guanosine diphosphate. The bound radioactivity was calculated using the methods previously mentioned.
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Animal Protocol |
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References |
Molecular Formula |
C24H27FN2O
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Molecular Weight |
378.482389688492
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Exact Mass |
378.21
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CAS # |
863513-93-3
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Related CAS # |
Cebranopadol; 863513-91-1
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Appearance |
Powder
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SMILES |
CN(C)C1(CCC2(CC1)C3=C(CCO2)C4=C(N3)C=CC(=C4)F)C5=CC=CC=C5
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InChi Key |
CSMVOZKEWSOFER-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C24H27FN2O/c1-27(2)23(17-6-4-3-5-7-17)11-13-24(14-12-23)22-19(10-15-28-24)20-16-18(25)8-9-21(20)26-22/h3-9,16,26H,10-15H2,1-2H3
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Chemical Name |
6-fluoro-N,N-dimethyl-1'-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine
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Synonyms |
GRT6005; GRT 6005; GRT-6005; Cebranopadol
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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 |
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) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.6421 mL | 13.2107 mL | 26.4215 mL | |
5 mM | 0.5284 mL | 2.6421 mL | 5.2843 mL | |
10 mM | 0.2642 mL | 1.3211 mL | 2.6421 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.
Duration of action of cebranopadol (12µg/kg) compared with fentanyl (9.4µg/kg) and morphine (1.9 mg/kg) after intravenous administration in the rat tail-flick test.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. th> |
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Analgesic effect of cebranopadol on spinal nerve ligation-induced mononeuropathic pain (SNL) and complete Freund’s adjuvant-induced chronic rheumatoid arthritic pain (CFA) 30 minutes after, and on tail flick-induced heat nociception (TF) 20 minutes after intravenous administration.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. td> |
Effect of intravenous cebranopadol on mechanical sensitivity in the ipsilateral and contralateral paws in a rat model of bone cancer pain.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. td> |
Antihyperalgesic activity of cebranopadol in streptozotocin (STZ)-treated and control rats measured as % MPE (mean ± S.E.M.;n= 10) by means of a paw pressure test in a model of STZ-induced diabetic polyneuropathy.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. th> |
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Effect of 1.0, 2.15, and 4.64 mg/kg i.p. J-113397 on the antihypersensitive effect of 1.7μg/kg i.v. cebranopadol (A) and 8.9 mg/kg i.v. morphine (B) in the spinal nerve ligation (SNL) model. Effect of 0.3 and 1.0 mg/kg i.p. naloxone on the antihypersensitive effect of 1.7μg/kg i.v. cebranopadol (C) and of 0.1, 0.3, and 1.0 mg/kg i.p.naloxone on the antihypersensitive effect of 8.9 mg/kg i.v. morphine (D) in the SNL model. Data are given as percentage of maximum possible effect (mean ± S.E.M.;n= 10) measured with an electronic von Frey filament based on the measurement of ipsilateral withdrawal thresholds 30 minutes after administration of cebranopadol or morphine.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. td> |
Antiallodynic effect of repeated daily intraperitoneal administration of cebranopadol or vehicle as measured by number of paw lifts from a cold plate during 2 minutes (mean ± S.E.M.;n= 13–15) (A) or % MPE (B) in the chronic constriction injury model.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. td> |
Dose-dependent effects of cebranopadol (A) and morphine (B) on motor coordination in rats.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. th> |
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Effects of cebranopadol (A and C) and morphine (B and D) on respiratory function in the whole-body plethysmography test in conscious rats.J Pharmacol Exp Ther.2014 Jun;349(3):535-48. td> |