Description

Pegsebrenatide, also known as NLY01, is a pegylated exendin-4-based GLP-1 receptor agonist engineered for extended half-life and enhanced blood–brain barrier (BBB) penetration. This unique design maintains GLP-1R agonism while enabling sustained receptor engagement and superior CNS access, differentiating it from conventional incretin analogues.

In neurodegenerative disease models—particularly Parkinson’s disease (PD)—Pegsebrenatide demonstrates potent neuroprotective and anti-inflammatory effects. By blocking microglia-mediated conversion of astrocytes into neurotoxic A1 phenotype, it protects dopaminergic neurons from degeneration. Preclinical Parkinson’s models show that Pegsebrenatide administration preserves motor function, reduces neuronal loss, and suppresses behavioral deficits.

The compound is produced in GMP-compliant facilities and purified to 95.50% purity, ensuring consistent delivery of high-quality peptide for preclinical research. Supplied as a lyophilized powder, Pegsebrenatide is well-suited for in vitro assays, rodent models, and neurodegeneration studies. Each batch includes a Certificate of Analysis (CoA) detailing purity, identity, and stability to support reproducibility.

Product Specifications

Mechanism of Action & Research Applications

Mechanism of Action

Pegsebrenatide is a GLP-1R agonist optimized for sustained activation and brain entry. By activating GLP-1 receptors, particularly on microglia and astrocytes, it intervenes in neuroinflammatory cascades. It prevents A1 astrocyte formation, a harmful reactive glial phenotype, and through that, protects dopaminergic neurons from degenerative processes commonly seen in PD.

Research Applications

• Parkinson’s Disease Models
  In multiple mouse models—including ?-synuclein PFF and hA53T transgenic mice—Pegsebrenatide preserves motor function and neuron viability, offering a tool for studying neuroprotective pathways.

• Glial Cell Modulation Studies
  Used to examine microglia-to-astrocyte signaling dynamics, cytokine profiles, and astrocyte reactivity, offering insights into neuroinflammation mechanisms.

• Neurodegeneration & Neuroprotection Research
  Investigates how GLP-1R agonism accelerates survival pathways, mitochondrial resilience, and reduction of neurotoxic glial responses.

• Drug Pharmacokinetics & Delivery
  Ideal for examining CNS-targeted pharmacotherapy effects, exploring dosing regimens, sustained release, and PEGylated peptide stability in animal models.

Development & Formulation Notes

• Reconstitution & Storage
  Reconstitute with sterile, endotoxin-free buffer to desired concentration (e.g., 1 mg/mL). Store aliquots at –20 °C or –80 °C to preserve activity; avoid repeated freeze–thaw.

• Dosing Strategies
  In rodent models, dose levels (e.g., 0.1–1 mg/kg, subcutaneously) should be calibrated based on pilot data. Monitor motor function and neuroprotection outcomes.

• Analytical Validation
  Include validation steps via HPLC or mass spectrometry for long-term stability studies. Check concentration and integrity periodically.

• Combination & Mechanistic Studies
  Combine Pegsebrenatide with anti-inflammatory agents, neurotrophic factors, or PD models to dissect additive or synergistic benefits.

  

Disclaimer

Pegsebrenatide (NLY01) is strictly for laboratory research use only. It is not intended for clinical, diagnostic, therapeutic, or veterinary use. Users must follow institutional safety and biosafety protocols.

Keywords

Pegsebrenatide; NLY01; GLP-1R agonist; long-acting peptide; BBB-penetrant GLP-1 analogue; PD neuroprotection; A1 astrocyte blockade; dopaminergic neuron preservation; neuroinflammation; GMP peptide.