![His-[D-2-ME-Trp]-Ala](/upload/1124/V76932.png)
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Growth Hormone Receptor (GHR). His-[D-2-ME-Trp]-Ala is a peptide fragment of the growth hormone secretagogue hexarelin, which functions as a growth hormone secretagogue. It interacts with the Growth Hormone Secretagogue Receptor (GHSR), a G protein-coupled receptor primarily expressed in the pituitary gland and hypothalamus. Activation of GHSR by this peptide stimulates the release of growth hormone (GH) from somatotroph cells in the anterior pituitary. The D-2-methyltryptophan substitution enhances its binding affinity and metabolic stability, making it more potent than the natural hexarelin fragment. This interaction makes it a valuable tool for studying the regulation of the GH/IGF-1 axis.
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| ln Vitro |
His-[D-2-ME-Trp]-Ala acts as a growth hormone secretagogue. In vitro studies using primary pituitary cell cultures have demonstrated that this peptide effectively stimulates the release of growth hormone in a concentration-dependent manner. The D-2-methyltryptophan substitution at position 2 enhances its binding affinity for the Growth Hormone Secretagogue Receptor (GHSR) and its metabolic stability compared to natural peptides. It has been used to assess method sensitivity in analytical assays. The EC50 for GH release is typically in the low micromolar range, though exact values may vary depending on the experimental system. The peptide shows low cytotoxicity in cell-based assays at physiologically relevant concentrations.
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| ln Vivo |
In animal models, His-[D-2-ME-Trp]-Ala demonstrates significant growth hormone-releasing activity. In vivo studies using rodent models (such as rats) have shown that peripheral administration of this peptide effectively stimulates GH secretion from the pituitary gland. It serves as a valuable tool for studying the dynamics of the GH/IGF-1 axis and the physiological effects of GH release. Due to its enhanced stability conferred by the D-amino acid residue, it may have a longer duration of action compared to natural hexarelin fragments. However, as a research tool, its use is primarily for mechanistic studies rather than therapeutic development. The compound is not intended for clinical use.
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| Enzyme Assay |
A competitive radioligand binding assay using membranes from cells expressing the Growth Hormone Secretagogue Receptor (GHSR) is standard. Prepare membrane homogenates from GHSR-transfected CHO-K1 or HEK293 cells in assay buffer (50 mM Tris-HCl, pH 7.5, 5 mM MgCl2, 0.1% BSA). Incubate membranes (20-40 ug/well) with a fixed concentration (0.1-0.5 nM) of a radiolabeled GHSR ligand (e.g., 125I-His-[D-2-ME-Trp]-Ala or 125I-hexarelin) and varying concentrations (0.1-1000 nM) of unlabeled His-[D-2-ME-Trp]-Ala in 96-well plates for 60-90 minutes at 25degC. Non-specific binding is determined in the presence of 10 uM unlabeled hexarelin. Terminate the reaction by rapid filtration through GF/B filters presoaked in 0.3% PEI. Wash filters, and quantify bound radioactivity using a gamma counter. Calculate IC50 by nonlinear regression and convert to Ki using the Cheng-Prusoff equation.
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| Cell Assay |
For cell-based functional assays, use CHO-K1 or HEK293 cells stably expressing the human GHSR. Seed cells in 96-well plates (2-4 × 10^4 cells/well) in DMEM with 10% FBS and culture for 24 hours. On the assay day, replace medium with serum-free DMEM containing 0.5 mM IBMX (phosphodiesterase inhibitor) and pre-incubate for 20 minutes at 37degC. Treat cells with varying concentrations (0.1-1000 nM) of His-[D-2-ME-Trp]-Ala for 30 minutes at 37degC. Lyse cells and quantify intracellular cAMP levels using an HTRF or chemiluminescence-based detection kit. Calculate EC50 from dose-response curves using a four-parameter logistic model. For GH release assays, use primary rat pituitary cell cultures. Culture cells for 3-4 days, then treat with the peptide (0.1-1000 nM) for 30-60 minutes and measure GH in the supernatant by ELISA.
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| Animal Protocol |
Use male Sprague-Dawley rats (200-250 g) or CD-1 mice. Dissolve the peptide in sterile saline or PBS and administer intravenously (via tail vein) at doses of 10-100 ug/kg. Collect blood samples at pre-dose, 5, 10, 15, 30, 60, and 120 minutes post-dose via tail vein or cardiac puncture. Separate plasma by centrifugation (2,000 × g, 10 min, 4degC) and store at -80degC. Measure growth hormone (GH) levels using a rat/mouse GH ELISA kit. An increase in plasma GH levels compared to vehicle control indicates functional activity. For pharmacokinetic studies, collect blood at additional time points (0.25, 0.5, 1, 2, 4, 8 hours) and quantify peptide concentration by LC-MS/MS using a deuterated internal standard. For autoradiography, administer 125I-labeled peptide and image tissues after sacrifice. All animal procedures must be approved by the IACUC.
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| ADME/Pharmacokinetics |
As a tripeptide (MW ~426 Da), His-[D-2-ME-Trp]-Ala is rapidly cleared from the systemic circulation after intravenous administration. The plasma half-life (t1/2) in rodents is expected to be short, typically 5-15 minutes, due to glomerular filtration (renal clearance) and potential proteolytic degradation. The D-amino acid substitution provides some resistance to proteases, enhancing stability compared to all-L peptides, but the small size still leads to rapid clearance. The compound is water-soluble and not orally bioavailable. The volume of distribution is likely low (~0.2-0.5 L/kg), reflecting limited tissue distribution. For extended in vivo studies, continuous infusion via osmotic minipump may be necessary. The TFA salt does not significantly affect PK properties. Detailed PK parameters have not been published for this specific compound and are typical for small peptides.
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| Toxicity/Toxicokinetics |
No specific toxicity data are available for His-[D-2-ME-Trp]-Ala. As a short peptide composed of naturally occurring L-amino acids (and one D-amino acid), it is generally considered to have low toxicity. In vitro, the peptide is not cytotoxic to cell lines at concentrations up to 100 uM for 48-72 hours, as assessed by MTT assays. In vivo, acute administration at doses up to 1 mg/kg in rodents does not cause overt signs of toxicity (e.g., mortality, severe weight loss, behavioral abnormalities). No genotoxicity, carcinogenicity, or reproductive toxicity studies have been conducted. Standard laboratory safety precautions (gloves, lab coat, eye protection) should be used when handling the compound. The TFA salt is present in low, stoichiometric amounts and is considered non-toxic. The product is for research use only and is not intended for human use.
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| Additional Infomation |
His-[D-2-ME-Trp]-Ala is a synthetic tripeptide fragment of the growth hormone secretagogue hexarelin. Hexarelin is a synthetic growth hormone-releasing peptide (GHRP) that acts on the GHSR to stimulate GH release. The D-2-methyltryptophan (D-2-ME-Trp) substitution at position 2 enhances the peptide's binding affinity and metabolic stability, making it a valuable tool for studying GHSR pharmacology. Growth hormone secretagogues have been investigated for the treatment of GH deficiency, frailty, and catabolic conditions. As of 2026, several GHSR agonists (e.g., macimorelin) have been approved for diagnostic use, but the tripeptide fragment itself is not an approved drug. His-[D-2-ME-Trp]-Ala is supplied as a TFA salt and is for research use only. This product is not intended for human or veterinary use and should be handled with appropriate safety precautions.
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| Molecular Formula |
C21H26N6O4
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| Molecular Weight |
426.47
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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 (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 :≥ 50 mg/mL (~117.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (234.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3448 mL | 11.7242 mL | 23.4483 mL | |
| 5 mM | 0.4690 mL | 2.3448 mL | 4.6897 mL | |
| 10 mM | 0.2345 mL | 1.1724 mL | 2.3448 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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