Semaglutide
Identification
| Property |
Value |
| CAS Number |
910463-68-2 |
| Molecular Formula |
C₁₈₇H₂₉₁N₄₅O₅₉ |
| Molecular Weight |
~4,113.6 Da |
| Sequence Length |
31 amino acids (engineered GLP-1 analog) |
| Appearance |
White to off-white lyophilized powder |
| Solubility |
Soluble in aqueous buffers at physiological pH |
Structural Features
Semaglutide is a structurally modified GLP-1 (7-37) analog engineered for extended pharmacokinetic half-life and resistance to enzymatic degradation:
| Modification |
Purpose |
| Aib⁸ (α-aminoisobutyric acid) |
Substitution at position 8 confers resistance to dipeptidyl peptidase-4 (DPP-4) cleavage |
| C18 fatty diacid linker |
Conjugated to Lys²⁶ via a gamma-glutamyl-2xOEG spacer; enables high-affinity, reversible albumin binding |
| Arg³⁴ substitution |
Replaces native Lys³⁴, preventing mis-acylation and improving manufacturing selectivity |
Half-Life Rationale
The C18 fatty diacid-albumin binding mechanism extends the circulating half-life to approximately 7 days in preclinical models, enabling once-weekly administration protocols. Albumin binding reduces renal clearance and protects the peptide from rapid proteolysis.
Comparator Analysis
| Parameter |
Semaglutide |
Tirzepatide |
Retatrutide |
| Receptor Target |
GLP-1R (selective) |
GIPR / GLP-1R (dual) |
GIPR / GLP-1R / GCGR (triple) |
| Molecular Weight |
~4,113.6 Da |
~4,813.5 Da |
~4,845.5 Da |
| Amino Acid Count |
31 |
39 |
39 |
| Half-Life |
~7 days |
~5 days |
~6 days |
| Synthesis Complexity |
High |
Very High |
Complex |
| DPP-4 Resistance |
Yes (Aib⁸) |
Yes |
Yes |
| Albumin Binding |
C18 fatty diacid |
C20 fatty diacid |
C20 fatty diacid |
Research Applications
Semaglutide is investigated across a broad range of metabolic research domains:
| Research Area |
Key Findings in Preclinical & Clinical Literature |
| Glucose Homeostasis |
Glucose-dependent insulin secretion enhancement; glucagon suppression during euglycemia and hyperglycemia |
| Body Weight Regulation |
Central and peripheral appetite suppression; delayed gastric emptying; reduced energy intake |
| Cardiovascular Outcomes |
MACE risk reduction in type 2 diabetes populations; systolic blood pressure improvement |
| NASH / MASLD |
Reduction in hepatic steatosis, lobular inflammation, and ballooning in biopsy-confirmed NASH |
| Renal Protection |
Reduction in albuminuria; attenuation of eGFR decline in chronic kidney disease |
| Neuroprotection |
Investigation in Parkinson's and Alzheimer's disease models via GLP-1R-mediated anti-inflammatory pathways |
Quality Specifications
| Parameter |
Specification |
Method |
| Purity (HPLC) |
≥99.0% |
Reverse-phase HPLC, 214 nm |
| Mass Identity |
MW ±1.0 Da |
ESI-MS or MALDI-TOF |
| Water Content |
≤5.0% |
Karl Fischer titration |
| Peptide Content |
≥80.0% |
Amino acid analysis |
| Linker Integrity |
Intact C18 fatty diacid conjugate (bulk orders) |
LC-MS characterization of intact conjugate |
| Trifluoroacetate |
≤0.1% (acetate salt form) |
Ion chromatography |
| Endotoxin |
≤1.0 EU/mg |
LAL kinetic chromogenic |
| Residual Solvents |
≤ ICH Q3C limits |
Headspace GC |
| pH |
5.0–7.5 (1 mg/mL) |
Potentiometric |
Linker Integrity Note: For bulk orders (>100 vials), a dedicated linker integrity verification by LC-MS is included in the standard quality package. This confirms the intact C18 fatty diacid conjugate, critical for pharmacological activity.
Available Configurations
| Format |
Size |
Vials per Kit |
| Standard Research Kit |
5 mg × 10 vials |
10 |
| Extended Research Kit |
10 mg × 10 vials |
10 |
| Custom Configuration |
Up to 25 mg/vial |
Per project scope |
Storage & Stability
| Condition |
Requirement |
| Short-term |
2–8°C, lyophilized form, protect from light |
| Long-term |
−20°C to −80°C, desiccated |
| Reconstituted |
24 h at 2–8°C; aliquot and freeze at −20°C for extended storage |
| Shipping |
Cold chain (2–8°C) recommended for international shipments; ambient acceptable for ≤7 days |
Documentation
- COA provided per batch with full chromatographic and mass spectrometric data
- MSDS supplied with each shipment
- Linker Integrity Report included for bulk orders (HPLC-MS confirmation of intact C18-fatty diacid conjugate)
Special Notes
- FOR LABORATORY RESEARCH USE ONLY.
- Aib⁸ incorporation increases synthetic complexity; batch-to-batch consistency is verified by HPLC-MS.
- The C18 fatty diacid linker is hydrophobic; reconstitution may require gentle agitation and pH adjustment.
Key Research References
| Reference |
PMID |
Key Finding |
| Lau J et al. "Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide." J Med Chem. 2015;58(18):7370–7380. |
26308095 |
Engineering of semaglutide with Aib⁸ substitution for DPP-4 resistance and C18 fatty diacid for albumin binding; 7-day half-life demonstrated |
| Marso SP et al. "Semaglutide and cardiovascular outcomes in patients with type 2 diabetes." N Engl J Med. 2016;375(19):1834–1844. |
27633186 |
SUSTAIN-6 trial: semaglutide reduced MACE outcomes in T2D; established cardiovascular benefit for GLP-1 RA class |
| Newsome PN et al. "A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis." N Engl J Med. 2021;384(12):1113–1124. |
33185364 |
Semaglutide significantly improved NASH resolution without worsening fibrosis in biopsy-confirmed NASH patients |
Stability & Storage
| Condition |
Degradation Profile |
| Lyophilized Storage |
Standard lyophilized peptide stability; no special handling beyond desiccated, temperature-controlled storage. 24 months at 2–8°C, 36 months at −20°C |
| Neutral pH (5.0–7.5) |
Stable; recommended pH for reconstitution and working solutions |
| Acidic pH (<4.0) |
May promote aggregation of the hydrophobic C18 linker; avoid strongly acidic buffers |
| Alkaline pH (>8.0) |
Risk of deamidation and C18 linker hydrolysis over extended periods |
| Temperature Stress |
The C18 fatty diacid linker is hydrophobic; can aggregate or precipitate under temperature fluctuations. Gentle agitation required during reconstitution |
| Reconstituted Solution |
24 h at 2–8°C; aliquot and freeze at −20°C for ≤30 days. Avoid repeated freeze-thaw |
Frequently Asked Questions
Q: What purity specifications apply to semaglutide?
≥99.0% by HPLC at 214 nm with ESI-MS mass identity confirmation (±1.0 Da). Additional QC includes peptide content (≥80.0%), water content (≤5.0%), and linker integrity verification by LC-MS for bulk orders. The Aib⁸ substitution and intact C18 fatty diacid conjugate are confirmed in every batch-specific COA.
Q: How should semaglutide be stored after reconstitution?
Reconstituted semaglutide is stable for 24 hours at 2–8°C. For longer storage, aliquot into single-use sterile vials and freeze at −20°C (stable ≤30 days). Do not store in alkaline buffers (pH > 8) which can cause deamidation and linker hydrolysis. The hydrophobic C18 linker may require gentle agitation during reconstitution — never vortex or shake vigorously. Avoid repeated freeze-thaw cycles.
Source & Purchase
For researchers requiring SEMAGLUTIDE with full analytical documentation including HPLC and LC-MS traces, visit the PeptideSourceHub product page for bulk pricing and specifications.
Purchase SEMAGLUTIDE with COA →
| Product |
Link |
| Tirzepatide (Dual GIP/GLP-1) |
tirzepatide.md — Dual GIPR/GLP-1R agonist |
| Retatrutide (Triple Agonist) |
retatrutide.md — Triple GIPR/GLP-1R/GCGR agonist |
| Cagrilintide (Amylin Analog) |
cagrilintide.md — Long-acting amylin receptor agonist |
| AOD-9604 (hGH Fragment) |
aod-9604.md — Lipolytic hGH fragment 177-191 |