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| 10mg |
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| Targets |
alpha-CGRP (human) primarily targets the calcitonin receptor-like receptor (CLR), which requires the receptor activity-modifying protein 1 (RAMP1) to form a functional CGRP receptor. This receptor is a G protein-coupled receptor (GPCR) that signals primarily through the Galphas pathway, leading to activation of adenylyl cyclase, increased cAMP production, and activation of protein kinase A (PKA). CGRP receptors are located on vascular smooth muscle cells, endothelial cells, and neurons.
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| ln Vitro |
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In vitro, alpha-CGRP (human) TFA exhibits potent vasodilatory effects. The analog Tyr-alpha-CGRP (human) TFA binds to membrane preparations from rat brain and spleen with IC50 values of 0.2 nM and 0.5 nM, respectively, demonstrating high receptor affinity. It induces positive chronotropic and inotropic effects in isolated guinea pig right and left atria with EC50 values of 282 nM and 74 nM, respectively. These properties make it a valuable tool for studying cardiovascular function and nociception. |
| ln Vivo |
In vivo, alpha-CGRP (human) TFA is a potent vasodilator that decreases blood pressure and increases heart rate upon peripheral administration. It is the most potent endogenous vasodilator identified to date and plays a critical role in the pathophysiology of migraine headaches, where elevated CGRP levels are found. Its effects on vascular tone and pain transmission are widely studied in models of cardiovascular disease and neurogenic inflammation. alpha-CGRP (human) TFA is also used as a standard in pharmacological assays.
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| Enzyme Assay |
For in vitro receptor binding assays, membrane preparations from rat brain (cerebellum and cerebral cortex) or spleen are incubated with [125I]-labeled CGRP (~0.05 nM) in the presence of increasing concentrations of unlabeled alpha-CGRP (0.001-1000 nM) in binding buffer (50 mM Tris-HCl, pH 7.4, 5 mM MgCl2, 0.1% BSA). Non-specific binding is determined using 1 microM unlabeled CGRP. After incubation at room temperature for 90-120 minutes, bound radioligand is separated by rapid filtration through GF/B filters pre-soaked in 0.3% polyethylenimine, and radioactivity is measured. Ki values are calculated by nonlinear regression analysis.
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| Cell Assay |
For functional cellular assays, cell lines expressing the human CGRP receptor (CLR/RAMP1), such as SK-N-MC neuroblastoma cells or HEK293 transfectants, are seeded in 96-well plates. Cells are loaded with a cAMP detection reagent (e.g., a bioluminescence resonance energy transfer (BRET)-based biosensor or a competitive ELISA kit). alpha-CGRP (0.001 nM to 1 microM) is added to the cells and incubated for 15-30 minutes at 37degC. cAMP accumulation is measured according to the manufacturer's instructions. The EC50 for cAMP stimulation is determined from dose-response curves. Forskolin (10 microM) can be used as a positive control.
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| Animal Protocol |
For in vivo hemodynamic studies, alpha-CGRP (human) TFA is dissolved in saline containing 0.1% BSA and administered intravenously (0.1-10 microg/kg) or intra-arterially to anesthetized rats or mice. Arterial blood pressure is measured using a catheter inserted into the carotid artery, and heart rate is monitored via ECG. Typically, alpha-CGRP produces a rapid, dose-dependent decrease in mean arterial pressure (MAP) and a reflex increase in heart rate. Peak effects occur within 1-2 minutes and return to baseline within 10-15 minutes. CGRP receptor antagonists can be co-administered to confirm receptor-mediated effects.
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| ADME/Pharmacokinetics |
As a 37-amino acid neuropeptide (molecular weight ~3789 Da), alpha-CGRP (human) TFA has a short plasma half-life due to rapid enzymatic degradation by neutral endopeptidase (NEP) and other proteases. The half-life in human plasma is approximately 7-10 minutes. After intravenous administration, the peptide is rapidly cleared from the circulation, primarily through the kidneys and enzymatic degradation in various tissues. It is not orally bioavailable. For research studies, it is typically administered via intravenous, subcutaneous, or intrathecal routes.
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| Toxicity/Toxicokinetics |
Toxicological data for alpha-CGRP (human) TFA are limited to cell-based and animal studies. In vitro assays at concentrations up to 10 microM show no direct cytotoxicity. In vivo, intravenous administration of alpha-CGRP at 1-10 microg/kg produces transient hypotension and tachycardia without significant organ toxicity. At very high doses (e.g., >100 microg/kg), prolonged hypotension may occur. Standard safety precautions should be followed when handling the peptide.
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| References |
[1]. Ambrish Kumar, et al. Protective Role of α-Calcitonin Gene-Related Peptide in Cardiovascular Diseases. Front Physiol. 2019 Jul 2;10:821.
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| Additional Infomation |
alpha-CGRP (human) TFA is a research-grade peptide and is not approved for clinical use. However, CGRP has been clinically validated as a target for migraine therapy; several small-molecule CGRP receptor antagonists (gepants) and monoclonal antibodies against CGRP or its receptor have been approved for migraine treatment. alpha-CGRP (human) TFA is used as a reference standard in quality control for these drugs. The free base CAS number is 90954-53-3. Store at -20degC as a lyophilized powder, protected from moisture and repeated freeze-thaw cycles.
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| Molecular Formula |
C165H268F3N51O51S2
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| Molecular Weight |
3903.33
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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 Note: (1). This product is not stable in solution, please use freshly prepared working solution for optimal results. (2). 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) |
H2O :~25 mg/mL (~6.40 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 | 0.2562 mL | 1.2810 mL | 2.5619 mL | |
| 5 mM | 0.0512 mL | 0.2562 mL | 0.5124 mL | |
| 10 mM | 0.0256 mL | 0.1281 mL | 0.2562 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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