Cebranopadol ((1α,4α)stereoisomer)

Alias: GRT6005; GRT 6005; GRT-6005; Cebranopadol

Cat No.:V3266 Purity: ≥98%

COA Product Data Instructions for use SDS

Cebranopadol 1α,4α-stereoisomer is a stereoisomer of cebranopadol.

Cebranopadol ((1α,4α)stereoisomer) Chemical Structure CAS No.: 863513-93-3
Product category: Opioid Receptor

This product is for research use only, not for human use. We do not sell to patients.

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Other Forms of Cebranopadol ((1α,4α)stereoisomer):

Cebranopadol

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Top Publications Citing lnvivochem Products

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Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

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Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Biological Data

Product Description

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.

Biological Activity I Assay Protocols (From Reference)

Targets

NOP Receptor/ORL1

ln Vitro

In vitro activity: Cebranopadol (also known as GRT-6005) is a newly developed, first-in-class drug that exhibits strong agonist activity on both the well-established mu opioid receptor and ORL-1 (an opioid receptor similar to -1). The analgesic nociceptin/orphanin FQ peptide (NOP) cebranopadol has ED50 values of 0.5-5.6 µg/kg after intravenous and 25.1 µg/kg after oral administration. It has demonstrated 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 trials in phases two and three are currently assessing its efficacy in treating both acute and chronic pain. Based on recent research, opioid and NOP receptor agonism may be used in conjunction as a novel treatment approach for cocaine addiction.

ln Vivo

Behavioral studies in pain models and pharmacokinetic evaluations were carried out in Sprague-Dawley rats (weight range 134−423 g); Iffa Credo, Brussels, Belgium provided the tail-flick model; Harlan Laboratories, Indianapolis, IN provided the bone cancer model; Janvier Laboratories, Le Genest Saint Isle, France provided the other pain models and pharmacokinetics); male rats were used in the majority of the experiments, with the exception of the bone cancer and tail-flick models, which used female Sprague-Dawley rats. Male Wistar rats, weighing between 150 and 375 grams, were used in side effect model studies (Depré, Saint Doulchard, France). The rats were kept in standard housing (20–24°C, 12 hours of light and dark, 35–70% relative air humidity, 10–15 air changes per hour, air movement<0.2 m/s), with unlimited access to food and water in their home cage. Except for mononeuropathy models, which required animals to undergo repeated testing with a minimum one-week washout period in between, all in vivo models only employed animals once. With the few exceptions listed below, animal testing was carried out in compliance with German Animal Welfare Law, the International Association for the Study of Pain's guidelines, and recommendations. The local government's animal research committee, which gets advice from a separate ethics committee, approved all study protocols. The treatment groups were assigned to the animals at random. Randomized tests were conducted using various doses and vehicles. The operators conducting the behavioral tests were unaware of the study hypothesis and the nature of drug differences, even though they were not formally "blinded" with regard to the treatment.

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.

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.

Animal Protocol

8.9 and 26.6 mg/kg s.c. for whole-body plethysmography test in conscious rats.

Sprague-Dawley rats

References

[1]. J Pharmacol Exp Ther . 2014 Jun;349(3):535-48.

[2]. J Pharmacol Exp Ther . 2017 Sep;362(3):378-384.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula	C24H27FN2O
Molecular Weight	378.482389688492
Exact Mass	378.21
CAS #	863513-93-3
Related CAS #	Cebranopadol; 863513-91-1
Appearance	Powder
SMILES	CN(C)C1(CCC2(CC1)C3=C(CCO2)C4=C(N3)C=CC(=C4)F)C5=CC=CC=C5
InChi Key	CSMVOZKEWSOFER-UHFFFAOYSA-N
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
Chemical Name	6-fluoro-N,N-dimethyl-1'-phenylspiro[4,9-dihydro-3H-pyrano[3,4-b]indole-1,4'-cyclohexane]-1'-amine
Synonyms	GRT6005; GRT 6005; GRT-6005; Cebranopadol
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)

Solubility Data

Solubility (In Vitro)

DMSO: >10mM

Water: <1 mg/mL

Ethanol:

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
(e.g. IP/IV/IM/SC)

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

(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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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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.

Note： (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.

Biological Data