Cebranopadol
(Synonyms: GRT6005) 目录号 : GC35637
A nociceptin-, µ-, ĸ-, and δ-opioid receptor agonist
Cas No.:863513-91-1
Sample solution is provided at 25 µL, 10mM.
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Cebranopadol is an agonist of nociceptin-, µ-, ĸ-, and δ-opioid receptor agonist (Kis = 0.9, 0.7, 2.6, and 18 nM, respectively).1 It is greater than 100-fold selective for these receptors over a panel of more than 100 ion channels, neurotransmitter transporters, receptors, and enzymes, but does bind to the serotonin (5-HT) receptor subtype 5-HT5A with a Ki value of 8.7 nM. Cebranopadol inhibits nociceptin-, DAMGO-, and SNC 80-induced GTPɣS binding in CHO cells expressing nociceptin-, µ-, and δ-opioid receptors, respectively (EC50s = 13, 1.2, and 110 nM, respectively), as well as U69,593-induced GTPɣS binding in HEK293 cells expressing the ĸ-opioid receptor (EC50 = 17 nM). It increases the paw withdrawal threshold in rat models of bone cancer pain and streptozotocin-induced diabetic neuropathy (ED50s = 3.6 and 0.5 µg/kg, respectively, i.v.). Cebranopadol also increases paw weight bearing on the ipsilateral side in a rat model of arthritis induced by complete Freund's adjuvant (CFA) and M. tuberculosis (ED50 = 5.5 µg/kg, i.v.).
1.Linz, K., Christoph, T., Tzschentke, T.M., et al.Cebranopadol: A novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonistJ. Pharmacol. Exp. Ther.349(3)535-548(2014)
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Kinase experiment: |
Human MOP, DOP, KOP, and NOP receptor binding assays are run in microtiter plates with wheat germ agglutinin-coated scintillation proximity assay beads. [N-allyl-2,3-3H]naloxone and [tyrosyl-3,5-3H]deltorphin II, [3H]Ci-977, and [leucyl-3H]nociceptin are used as ligands for the MOP, DOP, KOP, and NOP receptor binding studies, respectively. The KD values of the radioligands used for the calculation of Ki values are provided as supplemental information. The assay buffer used for the MOP, DOP, and KOP receptor binding studies is 50 mM Tris-HCl (pH 7.4) supplemented with 0.052 mg/mL bovine serum albumin. For the NOP receptor binding studies, the assay buffer used is 50 mM HEPES, 10 mM MgCl2, 1 mM EDTA (pH 7.4). The final assay volume of 250 μL/well included 1 nM [3H]naloxone, 1 nM [3H]deltorphin II, 1 nM [3H]Ci-977, or 0.5 nM [3H]nociceptin as a ligand and cebranopadol in dilution series. Cebranopadol is diluted with 25% DMSO 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 beads/well), which had been preloaded for 15 minutes at room temperature with 23.4 μg of human MOP membranes, 12.5 μg of human DOP membrane, 45 μg of human KOP membranes, or 25.4 µg of human NOP membranes per 250 µL of final assay volume. After short mixing, the assays are run for 90 minutes at room temperature. The microtiter plates are then centrifuged 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 [3H]naloxone-, [3H]deltorphin II-, [3H]Ci-977-, or [3H]nociceptin-specific receptor binding are calculated by nonlinear regression analysis. Individual experiments are run in duplicate and are repeated three times in independent experiments[1]. |
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Animal experiment: |
Rats[1] The pharmacokinetic properties of cebranopadol in rats are investigated after a single intravenous dose of 160 μg/kg cebranopadol. The intravenous dose is administered as a bolus in a volume of 2 mL/kg with a catheter in the vena femoralis. Blood samples (200 μL/sample) are withdrawn via an implanted arterial catheter (arteria carotis) by an automated blood sampling system at the following sampling times: 0 (predose), 5, 15, 30, 60, 180, 360, 720, and 1440 minutes after administration. Blood samples are centrifuged, and plasma is separated. Plasma concentrations of cebranopadol are determined using a validated liquid chromatography-tandem mass spectrometry method. The lower limit of quantification for cebranopadol in this method is 0.05 ng/mL using a sample volume of 50 µL of plasma. |
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References: [1]. Linz K, et al. Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist. J Pharmacol Exp Ther. 2014 Jun;349(3):535-48. |
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| Cas No. | 863513-91-1 | SDF | |
| 别名 | GRT6005 | ||
| Canonical SMILES | CN(C)[C@]1(C2=CC=CC=C2)CC[C@]3(C(N4)=C(CCO3)C5=C4C=CC(F)=C5)CC1 | ||
| 分子式 | C24H27FN2O | 分子量 | 378.48 |
| 溶解度 | DMSO: 6.67 mg/mL (17.62 mM); Water: < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
| General tips | 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液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet