![D[LEU4,LYS8]-VP TFA](/upload/1124/V77111.png)
| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
vasopressin V1b receptor[1]
D[LEU4,LYS8]-VP TFA acts as a selective agonist of the vasopressin V1b receptor. The binding affinity Ki values are 0.16 nM for the rat V1b receptor, 0.52 nM for the human V1b receptor, and 1.38 nM for the mouse V1b receptor. It displays significantly weaker binding to other receptors, with Ki values of 64 nM for the oxytocin receptor, 100 nM for the V2 receptor, and 3800 nM for the V1a receptor. |
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| ln Vitro |
The compound's selective agonism at the V1b receptor is confirmed via in vitro functional assays. D[LEU4,LYS8]-VP stimulates intracellular calcium mobilization in cells expressing the V1b receptor, leading to downstream activation of the protein kinase C (PKC) pathway. It exhibits weak antidiuretic (V2-mediated), pressor (V1a-mediated), and in vitro oxytocic activity compared to native arginine vasopressin (AVP), confirming its high selectivity for the V1b subtype.
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| ln Vivo |
In vivo studies demonstrate that D[LEU4,LYS8]-VP TFA activates the hypothalamic-pituitary-adrenal (HPA) axis via V1b receptors. In animal models, intravenous administration induces a dose-dependent increase in plasma ACTH (adrenocorticotropic hormone) and corticosterone levels. It shows significantly reduced pressor (blood pressure increasing) and antidiuretic effects compared to AVP, reflecting its V1b receptor selectivity. This compound is also used in metabolic studies investigating V1b-mediated control of insulin release.
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| Enzyme Assay |
The in vitro binding affinity of D[LEU4,LYS8]-VP is determined using radioligand competition binding assays. Membranes from cells expressing recombinant human, rat, or mouse V1b receptors are incubated with a radiolabeled vasopressin antagonist (e.g., [125I]-HO-LVA) in the presence of increasing concentrations of the test peptide. Non-specific binding is defined using excess unlabeled vasopressin. After incubation at room temperature for 60-90 minutes, bound radioactivity is separated by rapid filtration through glass fiber filters, and IC50 values are converted to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
Cyclic AMP (cAMP) accumulation assays are performed to assess V1b receptor activation. Cells expressing the V1b receptor are seeded in 96-well plates and pre-incubated with IBMX (a phosphodiesterase inhibitor). After treatment with D[LEU4,LYS8]-VP TFA or vehicle for 30 minutes, cells are lysed, and intracellular cAMP levels are measured using a competitive ELISA or HTRF-based kit. The EC50 for cAMP stimulation is calculated. Alternatively, calcium flux assays using fluorescent dyes (e.g., Fluo-4 AM) on a FLIPR system are used to measure rapid mobilization of intracellular calcium.
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| Animal Protocol |
In a typical rodent study, male rats or mice are anesthetized and fitted with indwelling jugular catheters for intravenous administration and blood sampling. D[LEU4,LYS8]-VP TFA is dissolved in saline and administered via bolus injection at doses ranging from 0.1-100 microg/kg. Blood samples are collected at various time points (e.g., 0, 5, 15, 30, 60 minutes) into EDTA-containing tubes kept on ice. Plasma is separated by centrifugation and stored at -80degC for subsequent ACTH or corticosterone measurement using specific immunoassay kits. Mean arterial pressure is monitored via a femoral artery catheter to assess pressor effects.
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| ADME/Pharmacokinetics |
Based on the parent peptide d[Leu4,Lys8]-VP, the compound is rapidly eliminated from circulation with a typical peptide half-life of 5-15 minutes due to proteolytic degradation. It has low oral bioavailability; thus, intravenous administration is preferred in pharmacological studies. The peptide does not cross the blood-brain barrier efficiently, but V1b receptors in peripheral tissues are accessible. The metabolic stability can be improved via cyclization or substitution, as seen in this analog.
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| Toxicity/Toxicokinetics |
The toxicity profile of D[LEU4,LYS8]-VP TFA is consistent with that of vasopressin peptide analogs. At high doses (≥100 microg/kg), it may induce mild, transient elevations in blood pressure due to residual V1a agonism, though these effects are significantly weaker than with AVP. No significant acute toxicity, hepatotoxicity, or nephrotoxicity has been reported within the typical effective dose range (0.1-30 microg/kg) in animal studies. Standard laboratory safety precautions should be followed.
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| References |
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| Additional Infomation |
D[LEU4,LYS8]-VP is the TFA salt form of a selective V1b receptor agonist, originally developed for research into stress, anxiety, and glucose homeostasis. It has not been approved for clinical therapeutic use and is strictly for research purposes only. The introduction of a deaminated cysteine at position 1 and Leu4 and Lys8 substitutions confers high receptor selectivity. This compound is an important tool for studying the functional distinction between V1a (vascular), V1b (pituitary/brain), and V2 (renal) vasopressin receptor subtypes.
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| Molecular Formula |
C49H68F3N11O13S2
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| Molecular Weight |
1140.25
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| Related CAS # |
D[LEU4,LYS8]-VP;42061-33-6
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| Appearance |
White to off-white solid powder
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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, avoid exposure to moisture. |
| 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) |
DMSO :≥ 100 mg/mL (~87.70 mM)
H2O :~100 mg/mL (~87.70 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.19 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8770 mL | 4.3850 mL | 8.7700 mL | |
| 5 mM | 0.1754 mL | 0.8770 mL | 1.7540 mL | |
| 10 mM | 0.0877 mL | 0.4385 mL | 0.8770 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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