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| 1mg |
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| 5mg |
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| Targets |
Apraglutide targets the glucagon-like peptide-2 receptor (GLP-2R), a G protein-coupled receptor expressed primarily in the gastrointestinal tract. The compound is a potent and highly selective GLP-2 agonist with EC50 values of 0.03 nM for the human GLP-2 receptor and 0.07 nM for the rat GLP-2 receptor. By activating the GLP-2 receptor, apraglutide promotes intestinal epithelial cell proliferation, reduces apoptosis, and enhances nutrient absorption. The receptor is also known as the GLP-2 receptor, and its activation leads to the release of various growth factors that support intestinal adaptation. Apraglutide's long-acting properties are achieved through specific amino acid substitutions that enhance its stability and resistance to proteolytic degradation.
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| ln Vitro |
Apraglutide demonstrates potent in vitro activity as a GLP-2 receptor agonist. The compound shows EC50 values of 0.03 nM for the human GLP-2 receptor and 0.07 nM for the rat GLP-2 receptor, demonstrating high potency and selectivity. In cell-based assays, apraglutide activates the GLP-2 receptor and stimulates downstream signaling pathways that promote cell proliferation and survival. The peptide's activity is concentration-dependent, with effects observed at picomolar to nanomolar concentrations. Apraglutide's long-acting properties are demonstrated in vitro through its resistance to degradation by dipeptidyl peptidase-4 (DPP-4) and other proteases. The compound's activity has been characterized in various cell-based systems using cells expressing the GLP-2 receptor.
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| ln Vivo |
Apraglotide (FE 203799; 5 mg/kg/dose administered subcutaneously twice on postoperative days 0 and 4) was administered to healthy, fecal fat and energy loss-free piglets. At day 7, the piglets displayed intestinal elongation, increased intestinal weight, longer villus height, and greater crypt depth [1].
In vivo, apraglutide has demonstrated significant efficacy in promoting intestinal adaptation and growth. In a neonatal piglet model of short bowel syndrome with total resection of the ileum, apraglutide enhanced adaptation and linear intestinal growth. The peptide promotes intestinal growth and enhances nutrient absorption, thereby reducing the dependency on parenteral nutrition in SBS patients. Apraglutide's long-acting properties allow for less frequent dosing compared to native GLP-2. The compound's in vivo activity has been characterized in various animal models of intestinal failure and short bowel syndrome. Its ability to promote intestinal adaptation makes it a promising therapeutic candidate for gastrointestinal disorders. |
| Enzyme Assay |
In vitro receptor binding assays for apraglutide involve measuring binding affinity to the GLP-2 receptor. Membranes from cells expressing the human or rat GLP-2 receptor are incubated with a radiolabeled GLP-2 ligand and varying concentrations of the test peptide. Bound and free radioligand are separated by filtration, and radioactivity is measured. Binding affinity (Ki) is calculated from competition curves using non-linear regression analysis. Alternatively, functional assays can measure receptor activation by assessing cAMP accumulation or other second messenger responses. EC50 values are calculated from dose-response curves. Each concentration is typically tested in duplicate or triplicate. Selectivity assays compare the compound's activity against related receptors.
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| Cell Assay |
In vitro cellular assays for apraglutide are performed using cells expressing the GLP-2 receptor. Commonly used cell lines include HEK293 or CHO cells stably expressing the human or rat GLP-2 receptor. Cells are treated with varying concentrations of apraglutide, and receptor activation is measured by cAMP accumulation using a homogeneous time-resolved fluorescence (HTRF) or AlphaScreen assay. Alternatively, cell proliferation assays can be performed using intestinal epithelial cell lines. The compound's ability to stimulate cell proliferation is measured using BrdU incorporation or CellTiter-Glo assays. Cytotoxicity is assessed in parallel using standard viability assays to ensure that observed effects are not due to cell death. EC50 values are calculated from dose-response curves.
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| Animal Protocol |
Animal/Disease Models: Newborn Duroc piglets, 2-5 days old, weighing 2-2.6 kg [1].
Doses: 5 mg/kg/dose. Mode of Route of Administration: subcutaneous injection, twice on the 0th and 4th day after surgery. Experimental Results: On day 7, treated piglets were healthy, had Dramatically diminished fecal fat and energy losses, and demonstrated intestinal elongation, greater small intestinal weight, longer villus height, and greater crypt depth. In vivo animal studies for apraglutide are conducted using models of short bowel syndrome and intestinal failure. A neonatal piglet model with total resection of the ileum has been used to evaluate the compound's effects on intestinal adaptation. Animals are administered apraglutide via subcutaneous injection at various doses and schedules. Intestinal length, weight, and histomorphology are assessed at study termination. Markers of cell proliferation (Ki-67) and apoptosis are measured by immunohistochemistry. Nutrient absorption is assessed using functional studies. Pharmacokinetic studies assess peptide concentrations in plasma. Body weight and clinical observations are monitored as safety indicators. Efficacy is expressed as improvement in intestinal adaptation and growth compared to vehicle-treated controls. |
| ADME/Pharmacokinetics |
Apraglutide exhibits pharmacokinetic properties characteristic of a long-acting peptide. The compound has a molecular formula of C172H263N43O52 and a molecular weight of 3765.25 g/mol. As a peptide, apraglutide is typically administered by subcutaneous injection. Its long-acting properties are achieved through amino acid substitutions that enhance resistance to proteolytic degradation. The compound has a prolonged half-life compared to native GLP-2, allowing for less frequent dosing. Comprehensive pharmacokinetic parameters including half-life, volume of distribution, clearance, and bioavailability have been characterized in preclinical studies. The peptide is soluble in water and other aqueous buffers. Its pharmacokinetic profile supports its use in preclinical studies of intestinal disorders.
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| Toxicity/Toxicokinetics |
Apraglutide is intended for laboratory research use only and has not undergone comprehensive clinical toxicology testing. As a GLP-2 analog, the compound would be expected to have effects on gastrointestinal cell proliferation and growth. Standard in vitro cytotoxicity assays in cell lines are typically performed alongside efficacy studies to rule out nonspecific toxicity. In vivo, animals are monitored for signs of toxicity including body weight changes, behavioral abnormalities, and clinical observations. Comprehensive toxicological characterization including genotoxicity, immunogenicity, and repeated-dose toxicity studies has been conducted as part of preclinical development. The compound's long-acting nature requires careful evaluation of potential effects on intestinal hyperplasia and neoplasia. Apraglutide is not approved for human use and is strictly intended for research purposes.
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| References | |
| Additional Infomation |
Apraglutide (FE 203799) is a novel, synthetic 33-amino-acid peptide and a long-acting analog of glucagon-like peptide-2 (GLP-2). It is a potent and highly selective GLP-2 receptor agonist with EC50 values of 0.03 nM for hGLP-2R and 0.07 nM for rGLP-2R. Apraglutide contains amino acid substitutions including Ala2>Gly, Met10>Ahx, Asn11>D-Phe, and Asn16>Leu. The peptide enhances intestinal adaptation and linear intestinal growth in a neonatal piglet model of short bowel syndrome. Apraglutide has not entered clinical trials and has not received regulatory approval for any indication. It is available from research chemical suppliers for non-clinical research purposes only. Apraglutide is a valuable research tool for studying GLP-2 biology and developing new therapies for intestinal failure and short bowel syndrome.
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| Molecular Formula |
C172H263N43O52
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| Molecular Weight |
3765.25
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| CAS # |
1295353-98-8
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| Related CAS # |
Apraglutide TFA
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| PubChem CID |
155559189
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
53
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| Hydrogen Bond Acceptor Count |
56
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| Rotatable Bond Count |
126
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| Heavy Atom Count |
267
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| Complexity |
8990
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| Defined Atom Stereocenter Count |
38
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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 (~26.56 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 | 0.2656 mL | 1.3279 mL | 2.6559 mL | |
| 5 mM | 0.0531 mL | 0.2656 mL | 0.5312 mL | |
| 10 mM | 0.0266 mL | 0.1328 mL | 0.2656 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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