Pegsebrenatide
Based on 1 Customer Validation
Pegsebrenatide (NLY01) is a blood-brain barrier-penetrant GLP-1R agonist. Pegsebrenatide alleviates retinal inflammation and neuronal death secondary to ocular hypertension. Pegsebrenatide significantly delays onset and reduces disease severity in experimental autoimmune encephalomyelitis. Pegsebrenatide inhibits the formation of A1 reactive astrocytes in nerve cells and reduces the loss of retinal ganglion cells and dopaminergic neurons. Pegsebrenatide exerts neuroprotective effects in a mouse model of Parkinson's disease by directly preventing microglia-mediated conversion of astrocytes to the A1 neurotoxic phenotype. Pegsebrenatide can be used for research on glaucoma, Parkinson's disease, and multiple sclerosis.
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- Purity: 95.50%
- CAS No.: 2243292-26-2
- 화학식: C₂₀₆H₃₁₈N₅₄O₆₉S₂(C₂H₄O)m+₂n; m≈₁₀; n≈₂₀
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보관:
Sealed storage, away from moisture and light, under nitrogen.
Powder -80°C, 2 years , -20°C, 1 year* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light, under nitrogen)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
Biological Activity
Pegsebrenatide (2 h) is a potent GLP1R agonist that induces cAMP production in GLP1R-transfected HEK293 cells[4].
Pegsebrenatide (1 μM) inhibits the increased expression levels of pro-inflammatory activation marker genes (Il1a, Il1b, Tnf, C1qa, Il6) and the elevated secretion of pro-inflammatory cytokines (IL-1α, TNFα, C1q) induced by α-syn PFF in mouse primary microglia, blocks α-syn PFF-induced conversion of mouse primary astrocytes to neurotoxic A1 reactive astrocytes, and thereby prevents α-syn PFF-ACM-induced death of mouse primary cortical neurons and dopaminergic neurons[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | Cmax | Tmax | MRT | AUCinf |
|---|---|---|---|---|---|---|---|
| Monkey[4] | 32 μg/kg | s.c. | 88 h | 52.7 ng/mL | 72 h | 114 h | 6833.5 ng·h/mL |
Pegsebrenatide (10 mg/kg; s.c.; twice weekly; 42 days) significantly delays EAE onset, attenuates disease severity, suppresses peripheral and CNS inflammation, and prevents RGC loss in chronic EAE[3].
Pegsebrenatide (NLY01) (3 mg/kg; s.c.; twice weekly; 5 months) exerts robust neuroprotective and behavioral rescue effects in the α-syn PFF mouse model of Parkinson's disease by inhibiting microglial activation and subsequent A1 astrocyte formation[4].
Pegsebrenatide (3 mg/kg; s.c.; twice weekly; until endpoint (10 months of age or death)) significantly extends survival and reduces neuropathological abnormalities in hA53T transgenic mice with familial α-synucleinopathy[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (adult, glaucoma induced by magnetic microbead injection into anterior chamber)[1]
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Dosage:5 mg/kg per injection
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Administration:subcutaneous; twice weekly; 14 or 42 days
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Result:Reduced Tnf mRNA upregulation in CD11b+ CD11c− cells at 14 days post-injection.
Reduced Il1a, Tnf, and C1qa mRNA upregulation in CD11b+ CD11c+ cells at 14 days post-injection.
Reduced expression of pan-reactive (Lcn2, Steap4, Gfap) and A1-specific (Serping1, Fkbp5, Amigo2) transcripts, and reduced C3 mRNA levels in ACSA2+ cells at 14 days post-injection.
Reduced Il1a, Tnf, and C1qa mRNA upregulation in both CD11b+ CD11c− and CD11b+ CD11c+ cells at 42 days post-injection.
Reduced expression of pan-reactive (Lcn2, Steap4, Gfap) and A1-specific (Serping1, Fkbp5, Amigo2) transcripts, and reduced C3 mRNA levels in ACSA2+ cells at 42 days post-injection.
Increased retinal ganglion cell (RGC) survival, with Brn3a+ RGC survival normalized to fellow control eyes reaching ~98% and Rbpms+ RGC survival normalized to fellow control eyes reaching ~100% at 42 days post-injection.
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Animal Model:C57BL/6J (9-week-old)[3]
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Dosage:10 mg/kg
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Administration:s.c.; twice weekly; 42 days
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Result:Significantly delayed EAE onset and attenuated disease severity, with a statistically significant reduction in cumulative clinical scores.
Significantly reduced spleen weight, absolute counts of CD45+ splenocytes, and absolute counts/percentages of CD11b+ myeloid cells (including CD11b+Ly6G+ neutrophils, CD11b+MHCII+ activated myeloid cells, and CD11b+CD11c+ dendritic cells) at PID 6.
Significantly reduced percentages/absolute counts of CD11b+MHCII+ activated myeloid cells and CD4+CD44+ effector/memory T cells in the spleen at PID 11.
Significantly reduced percentages of CD45 high infiltrating leukocytes, Clec12a+ monocytes, and CD4+CD44+ effector/memory T cells in the brain and spinal cord at PID 11.
Significantly reduced hindbrain expression of reactive astrocyte marker Lcn2 and chemokines Ccl8 and Cxcl1 at PID 11.
Significantly reduced retinal ganglion cell (RGC) loss (with more pronounced protection in central and peripheral retinal regions) at PID 42.
Significantly downregulated optic nerve expression of neurotoxic astrocyte genes (C3, Ligp1, Psmb8, H2-T23, H2-D1) and pro-inflammatory cytokine Tnfα at PID 42.
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Animal Model:C57BL/6 (mixed male and female, 3 months old, intrastriatal stereotaxic injection of α-synuclein preformed fibrils)[4]
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Dosage:3 mg/kg
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Administration:s.c.; twice weekly; 5 months
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Result:Significantly reduced p-α-synSer129 immunoreactivity in the striatum, ventral midbrain, and tyrosine hydroxylase (TH)-positive neurons.
Prevented α-syn PFF-induced loss of TH-positive and Nissl-positive neurons in the substantia nigra pars compacta (SNpc).
Normalized striatal dopamine levels and dopamine metabolite ratios.
Abolished α-syn PFF-induced ipsilateral amphetamine rotation.
Reduced deficits in the pole test, accelerating rotarod test, and cylinder test.
Restored grooming time and rearing behavior.
Reduced α-syn PFF-induced microglial activation (IBA1 immunoreactivity and density) in the SNpc.
Blocked α-syn PFF-induced astrocytic activation (GFAP immunoreactivity and protein levels) and formation of neurotoxic A1 astrocytes (C3d immunoreactivity and C3 mRNA expression) in the ventral midbrain.
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Animal Model:hA53T α-synuclein transgenic (C57BL/6, mixed male and female, 6 months old, familial Parkinson's disease model via constitutive expression of human A53T α-synuclein)[4]
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Dosage:3 mg/kg
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Administration:s.c.; twice weekly; until endpoint (10 months of age or death)
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Result:Prolonged lifespan by over 100 days.
Reduced p-α-synSer129 immunoreactivity, α-synuclein aggregation, and ubiquitin immunoreactivity in the lateral vestibular nucleus (LVe) of the brainstem.
Decreased levels of Triton X-100-insoluble α-synuclein and p-α-synSer129 in the brainstem.
Attenuated microglial activation (IBA1 immunoreactivity) and astrocytic activation (GFAP immunoreactivity) in brain tissue.
Chemical Information
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CAS No. 2243292-26-2
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Appearance Solid
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화학식 C₂₀₆H₃₁₈N₅₄O₆₉S₂(C₂H₄O)m+₂n; m≈₁₀; n≈₂₀
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Color White to off-white
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Synonyms
NLY01
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Sealed storage, away from moisture and light, under nitrogen
Powder -80°C 2 years -20°C 1 year * In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light, under nitrogen)
용액&용해도
H2O : ≥ 100 mg/mL
DMSO : 50 mg/mL (Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
* "≥" means soluble, but saturation unknown.
순도&문서
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Data Sheet (279 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
[1]. Sterling JK, et al. GLP-1 Receptor Agonist NLY01 Reduces Retinal Inflammation and Neuron Death Secondary to Ocular Hypertension. Cell Rep. 2020;33(5):108271. [Content Brief]
[2]. McGarry A, et al. Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2024;23(1):37-45. [Content Brief]
[3]. Gharagozloo M, et al. Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist, NLY01, in Experimental Autoimmune Encephalomyelitis. Neurotherapeutics. 2021;18(3):1834-1848. [Content Brief]
[4]. Yun SP, et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease. Nat Med. 2018;24(7):931-938. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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