TRV0109101
TRV0109101 is a μ-opioid peptide receptor (MOPR) selective agonist (KD = 70 nM) with blood-brain barrier permeability. TRV0109101 selectively promotes G protein signaling pathway coupling while reducing the recruitment of β-arrestin. TRV0109101 inhibits opioid-induced mechanical hyperalgesia and induces antinociceptive tolerance. TRV0109101 is applicable for pain-related research.
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- CAS 番号: 1401027-29-9
- 分子式: C21H28N2OS
- 分子量:356.53
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
[1]|
human μ-opioid receptor 70 nM (Kd) |
Arrestin-2/β-Arrestin 1 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | EC50 |
0.75 μM
Compound: (R)-19
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Agonist activity at human delta opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation by fluorescence assay
Agonist activity at human delta opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation by fluorescence assay
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[PMID: 24063433] |
| HEK293 | IC50 |
100 μM
Compound: (R)-19
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Inhibition of human Cav 1.2 ion channel expressed in HEK293 cells by whole-cell patch clamp technique
Inhibition of human Cav 1.2 ion channel expressed in HEK293 cells by whole-cell patch clamp technique
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[PMID: 24063433] |
| HEK293 | EC50 |
0.9 μM
Compound: (R)-19
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Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation by fluorescence assay
Agonist activity at human kappa opioid receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP accumulation by fluorescence assay
|
[PMID: 24063433] |
| HEK293 | IC50 |
>100 μM
Compound: (R)-19
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Inhibition of human Cav 1.2 ion channel expressed in HEK293 cells by whole-cell patch clamp technique
Inhibition of human Cav 1.2 ion channel expressed in HEK293 cells by whole-cell patch clamp technique
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[PMID: 24063433] |
| HEK293 | IC50 |
2.3 μM
Compound: (R)-19
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Inhibition of human ERG channel expressed in HEK293 cells by whole-cell patch clamp technique
Inhibition of human ERG channel expressed in HEK293 cells by whole-cell patch clamp technique
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[PMID: 24063433] |
| HEK293 | IC50 |
20 μM
Compound: (R)-19
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Inhibition of human Nav 1.5 tonic ion channel expressed in HEK293 cells by whole-cell patch clamp technique
Inhibition of human Nav 1.5 tonic ion channel expressed in HEK293 cells by whole-cell patch clamp technique
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[PMID: 24063433] |
| HEK293 | IC50 |
9 μM
Compound: (R)-19
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Inhibition of human Nav 1.5 phasic ion channel expressed in HEK293 cells by whole-cell patch clamp technique
Inhibition of human Nav 1.5 phasic ion channel expressed in HEK293 cells by whole-cell patch clamp technique
|
[PMID: 24063433] |
体外実験
TRV0109101 acts as a potent, G protein-biased, MOPR-selective agonist in HEK-293 cells, with an EC50 of 10 nM for cAMP inhibition[1].
TRV0109101 (41 nM-10 μM; 5 min) interacts with the orthosteric ligand binding site of human MOPR in HEK-293 cells, with an apparent KD of 70 nM in competition with DAMGO for β-arrestin2 recruitment[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
体内実験
TRV0109101 (20-40 mg/kg; s.c.; twice daily (days 1-3), single double dose (day 4); 5 days) does not induce opioid-induced mechanical allodynia in male C57BL/6 mice but does induce antinociceptive tolerance[1].
TRV0109101 (20 mg/kg; s.c.; twice daily; 7 days) rapidly reverses mechanical allodynia in male C57BL/6 mice, though antinociceptive tolerance still develops[1].
TRV0109101 (1-3 mg/kg; s.c.; twice daily) rapidly and fully reverses induced mechanical allodynia in male C57BL/6 mice, though antinociceptive tolerance still develops[1].
TRV0109101 (0.1-10 mg/kg; s.c.; single dose) produces dose-dependent antinociception in the mouse 56°C hot plate assay, with an ED50 of 1.1 mg/kg[1].
TRV0109101 (1-20 mg/kg; s.c.; single dose) produces dose-dependent inhibition of fecal boli accumulation in male C57BL/6 mice, with an ED50 of 6.3 mg/kg[1].
TRV0109101 (1-20 mg/kg; s.c.; single dose) produces dose-dependent inhibition of colonic motility in male C57BL/6 mice, with an ED50 of 9.4 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (8 to 10-week-old male, opioid-induced mechanical allodynia model via chronic minipump infusion of μ-opioid agonists over 7 days)[1]
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Dosage:20 mg/kg/day
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Administration:s.c.; continuous infusion; 7 days
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Result:Did not induce significant mechanical allodynia over the 7-day period.
Developed antinociceptive tolerance to thermal stimuli comparable to that seen with conventional opioids.
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Animal Model:C57BL/6 (8 to 10-week-old male, opioid-induced mechanical allodynia model via twice-daily subcutaneous dosing on days 1-3, with a double dose on day 4)[1]
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Dosage:20 mg/kg (days 1-3); 40 mg/kg (day 4)
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Administration:s.c.; twice daily (days 1-3); single double dose (day 4); 5 days
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Result:Did not develop opioid-induced mechanical allodynia over the 5-day treatment period.
Developed antinociceptive tolerance comparable to that seen with conventional opioids.
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Animal Model:C57BL/6 (8 to 10-week-old male, morphine-induced mechanical allodynia reversal model)[1]
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Dosage:20 mg/kg
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Administration:s.c.; twice daily; 7 days
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Result:Attenuated morphine-induced mechanical allodynia within 24 hours of treatment initiation, with levels indistinguishable from vehicle-treated animals.
Developed antinociceptive tolerance.
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Animal Model:C57BL/6 (8 to 10-week-old male, fentanyl-induced mechanical allodynia reversal model)[1]
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Dosage:1 mg/kg; 3 mg/kg
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Administration:s.c.; twice daily
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Result:Fully reversed fentanyl-induced mechanical allodynia within 1 day of treatment initiation at both doses, with levels indistinguishable from vehicle-treated animals by days 7-8.
Developed antinociceptive tolerance.
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Animal Model:C57BL/6 (8 to 10-week-old male, acute pain model via 56°C hot plate assay)[1]
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Dosage:0.1 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:s.c.; single dose
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Result:Produced dose-dependent antinociception, with an ED50 of 1.1 mg/kg.
Resulted in significant increases in percent maximum possible effect (%MPE) compared to vehicle at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg.
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Animal Model:C57BL/6 (8 to 10-week-old male, gastrointestinal function impairment model via fecal boli accumulation assay)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:s.c.; single dose
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Result:Produced dose-dependent reduction in fecal boli weight, with an ED50 of 6.3 mg/kg.
Resulted in significant decreases in fecal boli weight compared to vehicle at doses of 10 mg/kg and 20 mg/kg.
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Animal Model:C57BL/6 (8 to 10-week-old male, gastrointestinal function impairment model via glass bead colonic motility assay)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg; 20 mg/kg
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Administration:s.c.; single dose
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Result:Produced dose-dependent increases in colonic transit time, with an ED50 of 9.4 mg/kg.
Resulted in significant increases in transit time compared to vehicle at doses of 1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg.
化学情報
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CAS 番号 1401027-29-9
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分子量 356.53
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分子式 C21H28N2OS
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SMILES
C(CNCC1=CC=CS1)[C@@]2(CC3(OCC2)CCCC3)C4=CC=CC=N4
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Koblish M, et al. TRV0109101, a G Protein-Biased Agonist of the µ-Opioid Receptor, Does Not Promote Opioid-Induced Mechanical Allodynia following Chronic Administration. J Pharmacol Exp Ther. 2017;362(2):254-262. [Content Brief]
[2]. Chen XT, et al. Structure-activity relationships and discovery of a G protein biased μ opioid receptor ligand, [(3-methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the treatment of acute severe pain. J Med Chem. 2013;56(20):8019-8031. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
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