| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Angiotensin II receptor type 1 (AT1R).
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|---|---|
| ln Vitro |
A "gain-of-function" ligand, TRV056 is more effective than AngII at stimulating cellular Gq-mediated signaling, such as IP1 production, and has an allosteric coupling to Gq that is >10 times higher. "Gq-biased" AT1R agonists are more effective at stimulating Gq-mediated cellular signaling and allosterically promoting Gq coupling than the endogenous ligand angiotensin II (AngII)[1].
TRV056 is a "gain-of-function" ligand that demonstrates >10-fold greater allosteric coupling to Gq than Angiotensin II. It is highly efficacious in stimulating cellular Gq-mediated signaling (e.g., IP1 generation) while showing similar beta-arrestin coupling to AngII. |
| ln Vivo |
TRV056, as a Gq-biased agonist, has been used in vivo to study the distinct physiological roles of Gq versus beta-arrestin signaling downstream of AT1R. Its in vivo effects are primarily driven by Gq, distinguishing it from balanced agonists like AngII.
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| Enzyme Assay |
A competition binding assay is performed. Membranes from cells overexpressing AT1R are incubated with a radiolabeled antagonist (e.g., 125I-[Sar1,Ile8]-AngII). Varying concentrations of TRV056 are added, and the IC50 for displacing the radioligand is calculated to determine binding affinity.
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| Cell Assay |
HEK293 cells stably expressing AT1R are treated with TRV056 (0.1 nM-10 microM) for 1 hour. Gq activation is measured by quantifying the accumulation of IP1 (an inositol phosphate) using a homogeneous time-resolved fluorescence (HTRF) kit. This provides a measure of the compound's potency (EC50) for Gq activation.
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| Animal Protocol |
A standard in vivo protocol involves intravenous administration of TRV056 (e.g., 0.1-1 mg/kg) in normotensive or hypertensive rats. Blood pressure is monitored via a carotid artery catheter to assess the immediate hemodynamic effects driven by Gq signaling.
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| ADME/Pharmacokinetics |
As a small peptide, TRV056 is likely rapidly cleared from the circulation. Its PK profile is expected to be characterized by a short half-life and low oral bioavailability, typical for peptide-based research compounds.
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| Toxicity/Toxicokinetics |
Specific toxicity data for TRV056 is limited to in vitro cell viability assays. At the efficacious concentrations used for Gq activation (nM to low microM range), it shows no apparent cytotoxicity. High-dose in vivo toxicity has not been extensively characterized.
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| References | |
| Additional Infomation |
TRV056 is a research tool for dissecting AT1R signaling bias. It is part of a family of "TRV" biased ligands used to study angiotensin receptor pharmacology. It has not been advanced to clinical trials as a therapeutic agent for hypertension or heart failure.
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| Molecular Formula |
C52H74N14O13
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|---|---|
| Molecular Weight |
1103.22997140884
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| Exact Mass |
1102.555
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| CAS # |
812644-79-4
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| PubChem CID |
11205505
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| Appearance |
White to off-white solid powder
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| LogP |
-2.3
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| Hydrogen Bond Donor Count |
14
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
31
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| Heavy Atom Count |
79
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| Complexity |
2120
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| Defined Atom Stereocenter Count |
9
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| SMILES |
C(N1CCC[C@H]1C(=O)N[C@H](C(=O)O)CC1C=CC=CC=1)(=O)[C@@H](NC(=O)[C@]([H])([C@@H](C)CC)NC(=O)[C@@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC(=O)O)CC1C=CC(O)=CC=1)CC1NC=NC=1
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| InChi Key |
NOMIXRQBVMELPF-IWIOKYJLSA-N
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| InChi Code |
InChI=1S/C52H74N14O13/c1-5-29(4)43(49(76)62-37(23-32-25-56-27-59-32)50(77)66-20-10-14-39(66)47(74)63-38(51(78)79)22-30-11-7-6-8-12-30)65-46(73)36(21-31-15-17-33(67)18-16-31)61-48(75)42(28(2)3)64-40(68)26-58-45(72)35(13-9-19-57-52(54)55)60-44(71)34(53)24-41(69)70/h6-8,11-12,15-18,25,27-29,34-39,42-43,67H,5,9-10,13-14,19-24,26,53H2,1-4H3,(H,56,59)(H,58,72)(H,60,71)(H,61,75)(H,62,76)(H,63,74)(H,64,68)(H,65,73)(H,69,70)(H,78,79)(H4,54,55,57)/t29-,34-,35-,36-,37-,38-,39-,42-,43-/m0/s1
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| Chemical Name |
(3S)-3-amino-4-[[(2S)-1-[[2-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[(2S)-2-[[(1S)-1-carboxy-2-phenylethyl]carbamoyl]pyrrolidin-1-yl]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-4-oxobutanoic acid
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O: 1.96 mg/mL (1.78 mM)
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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 | 0.9064 mL | 4.5321 mL | 9.0643 mL | |
| 5 mM | 0.1813 mL | 0.9064 mL | 1.8129 mL | |
| 10 mM | 0.0906 mL | 0.4532 mL | 0.9064 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.
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