![[Dp-Cl-Phe6,Leu17]-VIP TFA](/upload/1124/V77344.png)
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IC50: 125.8 nM (VIP receptor)[1]
Vasoactive intestinal peptide (VIP) receptor. [D-p-Cl-Phe6,Leu17]-VIP acts as a specific antagonist for VPAC1 and VPAC2 (VIP receptors). It competitively binds to the VIP binding site, preventing the activation of the receptor by endogenous VIP. It is selective for VIP receptors, showing no activity on related class B GPCRs such as glucagon, secretin, or growth hormone-releasing factor (GRF) receptors. |
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| ln Vitro |
In vitro, [D-p-Cl-Phe6,Leu17]-VIP TFA is a highly potent VIP receptor antagonist with an IC50 of 125.8 nM. It effectively blocks VIP-induced cAMP accumulation, calcium mobilization, and smooth muscle relaxation in a dose-dependent manner. Importantly, it has no detectable agonist activity of its own and exhibits no activity on glucagon, secretin, or GRF receptors up to 10 uM, confirming its high selectivity for VIP receptors.
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| ln Vivo |
In vivo, [D-p-Cl-Phe6,Leu17]-VIP TFA is used to block the physiological actions of VIP in animal models. For example, in rodent models, it antagonizes VIP-induced pancreatic secretion, vasodilation, and bronchodilation. It is a crucial tool for demonstrating that certain physiological effects (e.g., regulation of exocrine pancreatic secretion, immune modulation) are specifically mediated by VIP receptors. The antagonist has a long duration of action in vivo due to the D-amino acid substitution, which confers resistance to proteolytic degradation.
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| Enzyme Assay |
A non-cell competitive binding assay is performed to determine antagonism. Membrane preparations from cells expressing VIP receptors (e.g., rat pancreatic acinar cells or CHO cells expressing VPAC1) are incubated with [125I]-VIP (a radiolabeled VIP ligand, 50-100 pM) and varying concentrations of the antagonist (0.01-1000 nM). After incubation at 25degC for 60 minutes, bound and free radioligand are separated by rapid filtration through GF/B filters. The radioactivity is counted, and the IC50 is calculated from the inhibition curve.
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| Cell Assay |
A functional cAMP accumulation assay is used to confirm antagonistic activity. Cells expressing VIP receptors are pre-incubated with [D-p-Cl-Phe6,Leu17]-VIP TFA (0.1-1000 nM) for 10-15 minutes. The cells are then stimulated with a submaximal concentration of VIP (e.g., 1-10 nM) in the presence of 1 mM IBMX (a phosphodiesterase inhibitor). After 30-60 minutes, the reaction is stopped, and intracellular cAMP levels are measured using a competitive ELISA or HTRF kit. The antagonist causes a rightward shift in the VIP dose-response curve (Schild analysis), allowing the pA2 value to be calculated.
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| Animal Protocol |
For in vivo studies, [D-p-Cl-Phe6,Leu17]-VIP TFA is typically administered intravenously (IV) or intraperitoneally (IP) at doses of 0.1-10 mg/kg. A typical protocol involves anesthetizing rats and measuring pancreatic secretion or blood pressure. After establishing baseline, the antagonist is administered as a bolus injection or continuous infusion, followed by a challenge dose of VIP. The reduction in VIP-induced physiological responses (e.g., stimulation of pancreatic juice flow, decrease in mean arterial pressure) is measured to quantify the degree of receptor blockade.
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| ADME/Pharmacokinetics |
[D-p-Cl-Phe6,Leu17]-VIP TFA is soluble in DMSO (100 mg/mL) and water. The TFA salt improves solubility. The D-p-Cl-Phe6 modification enhances stability against proteolytic degradation, resulting in a significantly longer plasma half-life compared to native VIP or its L-analogs. This allows it to effectively block VIP receptors for extended periods. For in vivo formulation, it can be dissolved in saline or DMSO/Tween 80/saline mixtures. Storage: lyophilized powder at -20degC; protect from moisture.
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| Toxicity/Toxicokinetics |
Toxicity data for [D-p-Cl-Phe6,Leu17]-VIP TFA is not extensively documented. As a selective antagonist of VIP receptors, it has no known intrinsic toxicity at the concentrations used for research. However, VIP is involved in multiple physiological processes, including vasodilation, bronchodilation, and immunomodulation. High doses of the antagonist could theoretically block these protective mechanisms. However, no significant adverse effects have been reported in the literature at typical research doses. The TFA salt is non-toxic.
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| References |
[1]. Pozo D, et, al. Characterization of VIP receptor-effector system antagonists in rat and mouse peritoneal macrophages. Eur J Pharmacol. 1997 Mar 5; 321(3): 379-86.
[2]. Pandol SJ, et, al. Vasoactive intestinal peptide receptor antagonist [4Cl-D-Phe6, Leu17] VIP. Am J Physiol. 1986 Apr; 250 (4 Pt 1): G553-7. [3]. Messmer B, et, al. Regulation of exocrine pancreatic secretion by cerebral TRH and CGRP: role of VIP, muscarinic, and adrenergic pathways. Am J Physiol. 1993 Feb; 264(2 Pt 1): G237-42. |
| Additional Infomation |
[D-p-Cl-Phe6,Leu17]-VIP TFA is a research-grade chemical tool widely used in gastrointestinal, cardiovascular, and respiratory pharmacology. It was first described in 1997 by Pozo et al. and is the standard reference antagonist for studying VIP receptor function. It is not a clinical drug and has no FDA approval. This product is used to characterize VIP receptor-effector systems, particularly in macrophages, pancreatic acinar cells, and smooth muscle. A key reference is Pozo D, et al. Eur J Pharmacol. 1997.
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| Molecular Formula |
C150H240F3CLN44O44
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| Molecular Weight |
3456.22
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| Related CAS # |
[D-p-Cl-Phe6,Leu17]-VIP;102805-45-8
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| Appearance |
Typically exists as solid at room temperature
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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 |
| 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2893 mL | 1.4467 mL | 2.8933 mL | |
| 5 mM | 0.0579 mL | 0.2893 mL | 0.5787 mL | |
| 10 mM | 0.0289 mL | 0.1447 mL | 0.2893 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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