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.
For research use only. We do not sell to patients.
- CAS No.: 1401027-29-9
- Formula: C21H28N2OS
- Molecular Weight:356.53
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Storage:Pure form -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
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
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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 | 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
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[PMID: 24063433] |
In Vitro
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. Further protocols information, click here.
In Vivo
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.
Chemical Information
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CAS No. 1401027-29-9
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Appearance Oil
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Molecular Weight 356.53
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Formula C21H28N2OS
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Color Colorless to off-white
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SMILES
C(CNCC1=CC=CS1)[C@@]2(CC3(OCC2)CCCC3)C4=CC=CC=N4
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Pure form -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 100 mg/mL (280.48 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.01 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.01 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocols
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Transepithelial/transendothelial electrical resistance assay
TEER measures electrical resistance across epithelial or endothelial monolayers cultured on permeable supports, and the readout reflects ionic conductance through the cell barrier, especially the paracellular pathway regulated by junctional integrity. TEER can be measured without destroying the monolayer and is commonly used before or during transport, permeability, barrier-disruption, and barrier-maturation experiments. TEER values are influenced by biological maturation and technical conditions; reported factors include temperature, medium formulation, passage number, electrode geometry, membrane properties, and junctional length during early monolayer maturation. Therefore, TEER should be interpreted with blank-insert subtraction, area normalization, repeated readings, and, when possible, orthogonal barrier readouts such as FITC-dextran flux or tight-junction staining.
Purity & Documentation
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Data Sheet (284 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[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]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.8048 mL | 14.0241 mL | 28.0481 mL | 70.1203 mL |
| 5 mM | 0.5610 mL | 2.8048 mL | 5.6096 mL | 14.0241 mL | |
| 10 mM | 0.2805 mL | 1.4024 mL | 2.8048 mL | 7.0120 mL | |
| 15 mM | 0.1870 mL | 0.9349 mL | 1.8699 mL | 4.6747 mL | |
| 20 mM | 0.1402 mL | 0.7012 mL | 1.4024 mL | 3.5060 mL | |
| 25 mM | 0.1122 mL | 0.5610 mL | 1.1219 mL | 2.8048 mL | |
| 30 mM | 0.0935 mL | 0.4675 mL | 0.9349 mL | 2.3373 mL | |
| 40 mM | 0.0701 mL | 0.3506 mL | 0.7012 mL | 1.7530 mL | |
| 50 mM | 0.0561 mL | 0.2805 mL | 0.5610 mL | 1.4024 mL | |
| 60 mM | 0.0467 mL | 0.2337 mL | 0.4675 mL | 1.1687 mL | |
| 80 mM | 0.0351 mL | 0.1753 mL | 0.3506 mL | 0.8765 mL | |
| 100 mM | 0.0280 mL | 0.1402 mL | 0.2805 mL | 0.7012 mL |
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