Glepaglutide | CAS 914009-86-2 | Long-Acting GLP-2 Receptor Agonist (Research Use Only) | Knowlux

Product Description

Glepaglutide (ZP1848), CAS 914009-86-2, is a synthetic 39-amino-acid long-acting analogue of human glucagon-like peptide-2 (GLP-2), supplied by Knowlux for laboratory research use. The peptide is a linear sequence incorporating nine amino acid substitutions relative to native hGLP-2(1-33) and a C-terminal hexalysine extension. The sequence is H-His-Gly-Glu-Gly-Thr-Phe-Ser-Ser-Glu-Leu-Ala-Thr-Ile-Leu-Asp-Ala-Leu-Ala-Ala-Arg-Asp-Phe-Ile-Ala-Trp-Leu-Ile-Ala-Thr-Lys-Ile-Thr-Asp-Lys-Lys-Lys-Lys-Lys-Lys-NH2. The molecular formula is C197H325N53O55 and the molecular weight is 4316.08 g/mol on a free-peptide basis. Each lot is released with a lot-specific COA, MSDS and analytical traceability.

CAS and Salt Form Clarification: CAS 914009-86-2 is the free peptide registry for Glepaglutide and is the identifier applied across the USAN Council statement, KEGG DRUG, MedChemExpress, TargetMol, PeptideDB, and ChemicalBook. The acetate salt circulates under the same CAS in commercial catalogues and is represented as C197H325N53O55.xC2H4O2 without a discrete acetate registry; Cayman Chemical and AbMole both list an acetate form under this CAS. The molecular formula C197H325N53O55 and molecular weight 4316.08 correspond to the free-peptide basis. The acetate counter-ion shifts the mass balance by approximately 60 g/mol per acetate, and one supplier lists the acetate as C199H329N53O57 with MW 4376.13, reflecting a diacetate assignment. Knowlux declares the salt form, acetate content, and peptide content per lot on the COA. Buyers should confirm whether the quoted material is free peptide or acetate salt before procurement, and should reconcile the molecular weight on the COA against the declared counter-ion basis rather than relying on the CAS number alone.

Structural and Design Note: Glepaglutide is not a fatty-acid-acylated peptide in the manner of semaglutide, and it does not contain a disulfide bond. Its extended duration of action derives from two design features acting in concert. First, nine amino acid substitutions relative to native GLP-2 confer resistance to DPP-4 cleavage and reduce chemical degradation liabilities, including oxidation and deamidation, while improving physical stability against aggregation and fibrillation. Second, the C-terminal hexalysine tail, referred to as Structure Inducing Probe technology, improves aqueous solubility and stability, enables a ready-to-use liquid formulation, and also improves synthetic yield. Upon subcutaneous administration, Glepaglutide forms a depot at the injection site and undergoes gradual C-terminal proteolytic cleavage to two principal metabolites: M1, 35 amino acids with loss of four C-terminal lysines, and M2, 34 amino acids with loss of five C-terminal lysines. Both metabolites retain full GLP-2 receptor potency comparable to the parent compound, and their slow release from the depot is the mechanistic basis for the extended pharmacological effect. The peptide contains a single tryptophan at position 26 as the principal UV chromophore and oxidation liability, and no methionine or cysteine.

Product Parameters

Product Details

1. Overview

Glepaglutide is a long-acting GLP-2 receptor agonist developed for the treatment of short bowel syndrome. Native human GLP-2 is a 33-residue intestinotrophic hormone with a circulating half-life of approximately 7 minutes, limited by rapid DPP-4 cleavage, chemical instability in aqueous solution, and a tendency to aggregate and fibrillate. Glepaglutide was engineered to address all three limitations simultaneously: the nine amino acid substitutions confer DPP-4 resistance and chemical and physical stability, while the C-terminal hexalysine tail enables a ready-to-use aqueous formulation and contributes to the depot mechanism. In clinical development, Glepaglutide has been evaluated in a Phase 2 trial in patients with short bowel syndrome, and it has been investigated in inflammatory bowel disease and Crohn's disease models. The material supplied under this specification is research-grade and is not intended for human administration.

2. Receptor Pharmacology and Pharmacokinetic Profile

Glepaglutide is a potent agonist at the GLP-2 receptor, the class B GPCR that mediates the intestinotrophic, reparative, and anti-inflammatory actions of the GLP-2 family. In preclinical models, Glepaglutide reduces faecal output, increases intestinal absorption, and alleviates small intestinal inflammation. In a rat model of small intestinal inflammation, Glepaglutide at 200 and 400 nmol/kg subcutaneously twice daily for 14 days produced a measurable intestinotrophic effect. The pharmacokinetic behaviour of Glepaglutide is dominated by depot formation at the subcutaneous injection site rather than by albumin binding. After injection, the peptide is gradually cleaved at the C-terminus to the M1 and M2 metabolites, both of which retain full GLP-2 receptor potency and are slowly released into circulation. This depot-and-metabolite mechanism produces an effective half-life of approximately 88 hours following a 10 mg subcutaneous dose, a profile that supports once-weekly dosing and distinguishes Glepaglutide from shorter-acting GLP-2 analogues such as teduglutide. The absence of a fatty acid chain and the reliance on the tail and amino acid substitutions for stability are the structural features that differentiate Glepaglutide from lipidated long-acting peptides in the metabolic disease space.

3. Research Applications

Published pharmacological characterizations and documented protocols describe the following research applications:

• GLP-2 receptor binding and functional agonist assays, including cAMP accumulation and intestinotrophic endpoints

• Short bowel syndrome research models, including faecal output, intestinal absorption, and adaptation

• Inflammatory bowel disease and Crohn's disease research models, including intestinal inflammation and cytokine profiling

• DPP-4 resistance and peptide stability studies, including comparative pharmacology with native GLP-2 and teduglutide

• Depot formation and metabolite profiling, including M1 and M2 cleavage products and their receptor potency

• Aqueous formulation development, including ready-to-use liquid stability and aggregation/fibrillation resistance

• Reference standard development for HPLC and LC-MS analytical methods

These descriptions are derived from published research and are provided for scientific reference only.

Quality Control

Solubility and Handling

Solubility: Glepaglutide solubility is solvent-dependent, and the aqueous and buffer values diverge in a practically important way. In water, AbMole and GLPBIO report solubility of 100 mg/mL (22.85 mM) for the acetate salt, with sonication and warming to 37C recommended to achieve dissolution; Fisher Scientific corroborates water solubility of >=50 mg/mL (11.58 mM) for the MedChemExpress grade. In PBS (pH 7.2), by contrast, Cayman Chemical reports only slight solubility (0.1-1 mg/mL) for its acetate salt. This divergence between water and PBS is consistent with the peptide's aqueous stability design and suggests that stock solutions should be prepared in water rather than in phosphate-buffered saline where high concentration is required. For practical stock preparation, water at 100 mg/mL with sonication and warming is the most consistently supported condition; PBS is suitable for lower-concentration working solutions but should not be assumed to support 100 mg/mL dissolution. Prepare solutions fresh and aliquot; general guidance for this peptide is to store stock solutions in tightly sealed vials and use within 1 month, avoiding repeated freeze-thaw cycles.

Handling Precautions: Use powder-handling containment, such as a glove box or fume hood with particulate control. Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. The Trp26 residue is the principal oxidation liability; protect from prolonged exposure to air and light. The peptide contains no cysteine or methionine, so reducing agents and methionine-oxidation protection measures are not required. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening.

Storage and Stability

Documentation Support

Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Salt-form identity, acetate content, water content, peptide content, and endotoxin data available on request. Custom specifications and third-party inspection can be arranged on a project basis.

About Knowlux

Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.

Compliance Statement

FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.

This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Glepaglutide has been investigated in clinical trials for short bowel syndrome but is not approved as a medicinal product in the United States or the European Union; the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.

Data Verification Notes

The molecular formula C197H325N53O55 and molecular weight 4316.08 are confirmed by the USAN Council statement, KEGG DRUG (mol weight 4316.01, exact mass 4313.4264), MedChemExpress, PeptideDB, TargetMol, and ChemicalBook. The USAN statement lists the molecular weight as 4318 Da, a rounding convention rather than a structural discrepancy; the 4316.08 value is adopted as the consensus calculated molecular weight. The sequence HGEGTFSSELATILDALAARDFIAWLIATKITDKKKKKK-NH2 is confirmed by KEGG DRUG, PeptideDB, ChemicalBook, and the FDA UNII preferred substance name. The nine amino acid substitutions and the C-terminal hexalysine tail are described in the USAN chemical name and the Journal of Medicinal Chemistry design paper. The absence of lipid modification and disulfide bonds is explicitly stated in the molecular structure compilation. The M1/M2 metabolite and depot mechanism are from the same structure compilation, citing the design paper. The solubility values, water 100 mg/mL and PBS 0.1-1 mg/mL, are from AbMole/GLPBIO and Cayman, respectively. Storage guidance is consistent across AbMole, InvivoChem, Adooq, and TargetMol and is reported as-is.

Formatting Note: All formulas, sequences, and comparison operators use plain ASCII notation to prevent character corruption on the platform. Section headings, table alignment, and spacing follow the approved product detail pattern. No trailing spaces or non-breaking characters are used; tables use consistent pipe alignment. No web links or hyperlinks are included in this document.