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Semaglutide | CAS: 910463-68-2

CAS Number:
910463-68-2
Chemical Classification:
Research peptide

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Semaglutide is a lipidated glucagon-like peptide-1 receptor agonist that has become a standard pharmacological reference for selective incretin signaling in metabolic laboratories. Registered under CAS 910463-68-2, the analog resists dipeptidyl peptidase-4 cleavage and binds serum albumin, properties that make it well suited to half-life and receptor-occupancy studies spanning several hours. Research objectives vary considerably across groups—some isolate beta-cell insulin granule dynamics, others map vagal contributions to gastric emptying, and still others compare signaling bias relative to native GLP-1. Typical experimental deployments include stable GLP-1R cell-line dose–response assays, islet perifusion under graded glucose, and rodent gastric transit protocols with tracer readouts. Analytical batches are characterized by COA, LC-MS, HPLC, and NMR documentation; material is supplied for academic and biotech laboratory use only.

CAS
910463-68-2
Molecular Formula
C187H291N45O59
Molecular Weight
4113.6 g/mol
Purity
≥98%
Appearance
White lyophilized powder
Storage
Store at -20°C, desiccated

Analytical Documentation

COA✓ Available
LC-MS✓ Available
HPLC✓ Available
NMR✓ Available

Research Inquiry

Overview

Semaglutide is a modified 31-amino-acid peptide analog of glucagon-like peptide-1 engineered for enhanced enzymatic stability and prolonged receptor engagement in research settings. The sequence incorporates an alpha-aminoisobutyric acid at position 2 to resist dipeptidyl peptidase-4 cleavage, plus a large C-terminal fatty acid conjugate that promotes albumin binding and extended half-life in pharmacokinetic studies. Semaglutide functions as a selective GLP-1 receptor agonist within the incretin peptide family, enabling investigators to model postprandial insulinotropic signaling without simultaneous GIP receptor activation. Its molecular design has made it a benchmark ligand for studying GLP-1R biased signaling, gastric emptying kinetics, and central nervous system penetration of lipidated incretin analogs in preclinical research platforms. Supplied at ≥98% purity (C187H291N45O59; 4113.6 g/mol), this material supports controlled laboratory investigation under research-use-only conditions.

Mechanism of Action

Semaglutide binds GLP-1R and triggers Gs-mediated adenylyl cyclase activation, raising intracellular cAMP and PKA-dependent phosphorylation of targets involved in insulin granule exocytosis in pancreatic beta cells. In enteroendocrine L cells, autocrine GLP-1R loops modulate peptide secretion dynamics, while vagal afferent activation contributes to slowed gastric emptying observed in rodent and ex vivo perfusion models. Hepatic glucose production is indirectly attenuated through combined hyperinsulinemia and reduced glucagon tone rather than direct GLP-1R expression on hepatocytes. Central GLP-1R populations in the hypothalamus and brainstem integrate semaglutide-associated signals with energy balance pathways when the peptide crosses the blood-brain barrier in research dosing paradigms. Lipidation kinetics influence free fraction and receptor occupancy over multi-hour experimental windows.

Receptor Binding & Signaling

Semaglutide exhibits high affinity and full agonism at the human GLP-1 receptor in recombinant cell systems, with negligible activity at GIPR, glucagon receptor, or amylin receptor at concentrations used in standard metabolic research assays. Albumin binding reduces the unbound peptide pool, altering apparent potency in plasma-containing media compared with serum-free cell culture. Beta-arrestin recruitment and receptor internalization profiles differ from native GLP-1, supporting studies of biased agonism and downstream transcriptomic consequences. Radioligand competition and surface plasmon resonance experiments confirm orthosteric engagement with species-specific affinity differences between human and rodent GLP-1R orthologs.

Research Applications

GLP-1R cAMP and secretion assays

Semaglutide is a reference agonist in stable cell lines expressing human GLP-1R for cAMP accumulation, beta-arrestin biosensor, and internalization readouts. Islet perifusion experiments use the peptide to benchmark insulin secretion rates against native GLP-1 and other analogs with distinct lipidation. Dose-response curves establish EC50 values for batch release testing and inter-laboratory comparability. Researchers pair semaglutide with DPP-4 inhibitors or receptor antagonists to validate pathway specificity. These assays focus on quantitative pharmacology rather than therapeutic outcome modeling.

Gastric emptying and gut motility models

In rodent gastric emptying studies and ex vivo intestinal transit preparations, semaglutide slows nutrient delivery through GLP-1R-dependent vagal and enteric mechanisms. Investigators measure acetaminophen absorption kinetics, bead transit times, or antral contractility patterns after controlled peptide administration in research protocols. GLP-1R knockout animals help attribute effects to receptor-specific signaling. Semaglutide enables comparison with dual incretin agonists to isolate GLP-1-only contributions to gastrointestinal physiology. Results inform mechanistic diagrams of gut-brain axis regulation in metabolic science.

Central GLP-1R neuroscience platforms

Semaglutide supports research on hypothalamic and brainstem GLP-1R neurons using c-Fos mapping, electrophysiology, and cerebrospinal fluid sampling in animal models. Lipidation facilitates sustained receptor activation relevant to studying appetite-related neuropeptide expression and reward circuit modulation in controlled experiments. Central versus peripheral administration routes distinguish autonomic from direct neural effects. Semaglutide serves as a tool compound in comparisons with non-lipidated GLP-1 analogs for blood-brain barrier penetration assessments. Studies remain confined to preclinical neuroscience research frameworks.

Cardiovascular and renal signaling studies

Ex vivo heart and kidney preparations expose tissues to semaglutide to evaluate GLP-1R expression in non-classical metabolic organs. Researchers measure natriuresis markers, endothelial nitric oxide pathways, and inflammatory cytokine profiles in cell culture models of renal tubular and vascular endothelial cells. Semaglutide helps determine whether GLP-1R activation modifies stress-response pathways independent of glycemic changes when glucose is clamped in paired experiments. These exploratory platforms extend incretin biology beyond pancreatic endpoints in basic research.

Molecular Information

Sequence & Chain Summary

31-amino-acid GLP-1 analog (positions aligned to native GLP-1 sequence).

Modification Type

Aib at position 2; C18 fatty di-acid via gamma-Glu linker at Lys20.

Structural Notes

Semaglutide maintains the alpha-helical motif required for GLP-1R N-terminal domain engagement, with the fatty acid extending hydrophobic interaction with serum albumin. Mass spectrometric confirmation requires deconvolution of lipid heterogeneity when multiple fatty acid species are present in synthesis batches. The peptide's large molecular weight challenges standard HPLC column loading, necessitating adjusted gradient methods. Helical content remains stable in phospholipid bicelles used for structural biology research. Purity assessment combines RP-HPLC with peptide mapping after enzymatic digest. Batch-specific molecular characterization—including mass confirmation and purity profiling—is available through COA, LC-MS, HPLC, and NMR documentation supplied with Semaglutide.

Molecular Formula
C187H291N45O59
Molecular Weight
4113.6 g/mol
Purity Specification
≥98%

Experimental Notes

Stability

Lyophilized semaglutide stored desiccated at −20°C retains activity over prolonged archival periods. Reconstituted solutions are susceptible to aggregation and adsorption to glass and plastic; low-bind consumables are recommended. Minimize time at room temperature during assay setup. pH 7.4 buffers generally preserve solubility for same-day experiments. Follow lot-specific COA guidance for reconstituted aliquot storage duration. Lyophilized Semaglutide should be protected from repeated freeze-thaw cycles, moisture, and prolonged exposure to ambient light where applicable. Analytical integrity is best preserved when material is stored under the conditions specified on the certificate of analysis.

Storage Conditions

Store at -20°C, desiccated. Semaglutide is supplied as white lyophilized powder. For long-term archival storage in research inventories, maintain sealed containers with desiccant where recommended and document lot numbers for traceability across experimental runs.

Laboratory Handling

Reconstitute with bacteriostatic or sterile water depending on assay requirements. Centrifuge vials briefly before opening to collect lyophilized material. Avoid vigorous vortexing that may promote foaming and surface denaturation. Shield from direct light during prolonged bench work. Record peptide concentration using validated UV or LC-MS methods for experimental reproducibility. Reconstitute only with appropriate research-grade solvents compatible with your assay format. Allow vials to reach equilibrium before opening, work under clean bench conditions, and label all working solutions with concentration, date, and researcher ID per institutional SOPs.

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Frequently Asked Questions

Research-focused answers about Semaglutide. For laboratory use only — not medical advice.

What is Semaglutide used for in research?
Semaglutide is intended for in vitro and in vivo research examining GLP-1 receptor pharmacology, incretin signaling, and related metabolic pathways in qualified laboratory environments. It is not for human consumption, clinical application, or compounding into products for administration. Users must comply with institutional research safety policies and applicable regulations governing research chemicals.
How does Semaglutide work biologically?
Semaglutide activates GLP-1 receptors to increase cAMP, enhance glucose-dependent insulin secretion, reduce glucagon release, and slow gastric emptying in experimental models. C-terminal lipidation prolongs peptide availability in pharmacokinetic research compared with native GLP-1.
What receptors does Semaglutide interact with?
The primary target is the glucagon-like peptide-1 receptor (GLP-1R). At standard research concentrations, meaningful activation of GIPR, glucagon receptor, or unrelated class B receptors is not observed in validated selectivity panels.
Is Semaglutide stable at room temperature?
Lyophilized semaglutide stored desiccated at −20°C retains activity over prolonged archival periods. Reconstituted solutions are susceptible to aggregation and adsorption to glass and plastic; low-bind consumables are recommended. Minimize time at room temperature during assay setup. pH 7.4 buffers generally preserve solubility for same-day experiments. Follow lot-specific COA guidance for reconstituted aliquot storage duration. For short-term laboratory workflows, minimize time at room temperature and return unused material to recommended storage promptly. Semaglutide is not formulated for ambient long-term storage.
What is the recommended storage condition for Semaglutide?
Store at -20°C, desiccated. Store lyophilized material in a dedicated −20°C freezer, protect from moisture ingress, and avoid repeated temperature cycling. Reconstituted solutions should be aliquoted and frozen if not used within the validated window of your internal stability study.