Tirzepatide
Identification
| Property |
Value |
| Molecular Formula |
C₂₂₅H₃₄₈N₄₈O₆₈ |
| Molecular Weight |
~4,813.5 Da |
| Amino Acid Count |
39 |
| Appearance |
White to off-white lyophilized powder |
| Solubility |
Soluble in aqueous buffers; reconstitution may require gentle agitation due to lipophilic C20 fatty diacid linker |
| Receptor Targets |
GIPR / GLP-1R (dual agonist) |
Structural & Pharmacological Profile
Tirzepatide is a first-in-class dual GIP and GLP-1 receptor agonist. Its design incorporates an imbalanced agonist profile, with greater potency at the GIP receptor relative to the GLP-1 receptor. The C20 fatty diacid moiety conjugated via a linker to Lys²⁰ provides extended pharmacokinetics through albumin binding.
Key Structural Features
| Feature |
Detail |
| Peptide Backbone |
39-amino acid linear peptide based on GIP sequence with GLP-1 activity-optimizing substitutions |
| Fatty Acid Moiety |
C20 eicosanedioic acid (icosanedioic acid) |
| Linker Chemistry |
gamma-Glu-2xOEG (gamma-glutamyl-bis-ethylene glycol) spacer to Lys²⁰ |
| DPP-4 Resistance |
Engineered sequence prevents rapid enzymatic cleavage |
| Half-Life |
~5 days in preclinical models |
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 |
| Clinical BW Reduction |
~14.9% (STEP 1, 68 wk) |
~22.5% (SURMOUNT-1, 72 wk) |
~24.2% (Ph2, 48 wk) |
| Synthesis Complexity |
High |
Very High |
Complex |
| Half-Life |
~7 days |
~5 days |
~6 days |
| Fatty Acid Linker |
C18 fatty diacid |
C20 fatty diacid |
C20 fatty diacid |
| Receptor Bias |
GLP-1R only |
GIPR > GLP-1R |
Balanced triple agonism |
Clinical data cited from published trial results in peer-reviewed literature. Comparative efficacy figures are derived from distinct trial populations and protocols; direct cross-trial comparisons should account for differences in study design, duration, and population characteristics.
Research Applications
| Research Domain |
Description |
| Metabolic Regulation |
Investigation of dual incretin receptor agonism on glucose-dependent insulin secretion, glucagon suppression, and insulin sensitivity |
| Body Weight & Adiposity |
Preclinical and clinical studies demonstrating substantial body weight reduction via combined central and peripheral mechanisms |
| Cardiovascular Outcomes |
HFpEF outcomes; blood pressure and lipid profile improvements |
| NASH / MASLD |
Significant histological improvement in MASH resolution without worsening of fibrosis |
| Renal Outcomes |
Reduction in albuminuria and composite renal endpoints in type 2 diabetes |
| Obstructive Sleep Apnea |
Investigated as adjunct therapy; weight-loss-mediated improvement in AHI |
Quality Specifications
| Parameter |
Specification |
Method |
| Purity (HPLC) |
≥99.0% |
RP-HPLC, C18 column, 214 nm |
| Mass Identity |
MW ±1.0 Da |
ESI-MS |
| Water Content |
≤5.0% |
Karl Fischer titration |
| Peptide Content |
≥80.0% |
Amino acid analysis |
| Counterion |
Acetate form (≤1.0% TFA) |
Ion chromatography |
| Endotoxin |
≤1.0 EU/mg |
LAL kinetic chromogenic |
| Residual Solvents |
≤ ICH Q3C limits |
Headspace GC |
| pH (1 mg/mL) |
5.0–7.5 |
Potentiometric |
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 |
Bulk/custom sizes |
Per project |
Storage & Stability
| Condition |
Requirement |
| Short-term Storage |
2–8°C, lyophilized form |
| Long-term Storage |
−20°C to −80°C |
| Light Protection |
Store in amber vials or opaque containers |
| Reconstituted |
24 h at 2–8°C; −20°C for longer-term aliquots |
| Shipping |
Cold chain (2–8°C) recommended; ambient acceptable ≤7 days |
Documentation
- COA per batch: HPLC purity chromatogram, MS spectrum, quantitative data
- MSDS per shipment
- C20 Linker Integrity Report included with bulk orders
Special Notes
- FOR LABORATORY RESEARCH USE ONLY.
- Tirzepatide synthesis complexity is rated Very High due to the 39-amino acid sequence length, C20 fatty acid conjugation, and multiple non-proteinogenic modifications. Batch-to-batch consistency is assured through rigorous HPLC-MS characterization.
- Dual agonism research protocols should consider receptor occupancy and signaling bias when designing comparative experiments.
Key Research References
| Reference |
PMID |
Key Finding |
| Coskun T et al. "LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept." Mol Metab. 2018;18:3–14. |
30473097 |
Preclinical characterization of tirzepatide demonstrating dual GIPR/GLP-1R agonism with imbalanced activity favoring GIPR; superior glycemic and weight reduction vs selective GLP-1R agonism |
| Jastreboff AM et al. "Tirzepatide once weekly for the treatment of obesity." N Engl J Med. 2022;387(3):205–216. |
35658024 |
SURMOUNT-1 pivotal trial: tirzepatide produced up to 22.5% body weight reduction at 72 weeks in participants with obesity |
| Frias JP et al. "Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes." N Engl J Med. 2021;385(6):503–515. |
34170647 |
SURPASS-2: head-to-head comparison demonstrating superior HbA1c and body weight reductions vs semaglutide 1.0 mg |
Stability & Storage
| Condition |
Degradation Profile |
| Lyophilized Storage |
Standard lyophilized peptide stability; desiccated, temperature-controlled storage. 24 months at 2–8°C, 36 months at −20°C |
| Neutral pH (5.0–7.5) |
Stable; recommended for reconstitution and working solutions |
| Acidic pH (<4.0) |
May promote aggregation of the hydrophobic C20 linker; avoid acidic buffers |
| Alkaline pH (>8.0) |
Risk of deamidation and C20 linker hydrolysis over extended incubation |
| Temperature Stress |
C20 fatty diacid linker is hydrophobic; aggregation/precipitation possible with temperature fluctuations. Gentle agitation during reconstitution recommended |
| 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 tirzepatide?
≥99.0% by HPLC at 214 nm with ESI-MS mass identity confirmation (±1.0 Da). Comprehensive QC includes peptide content (≥80.0%), water content (≤5.0%), TFA content (≤1.0%) via ion chromatography, and linker integrity verification. The C20 fatty diacid conjugate is confirmed intact in every batch-specific COA.
Q: How should tirzepatide be stored after reconstitution?
Reconstituted tirzepatide 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). The C20 fatty diacid linker is highly hydrophobic — gentle agitation may be required during reconstitution. Never vortex. Avoid strongly acidic (pH < 4) or alkaline (pH > 8) buffers. Do not subject to repeated freeze-thaw cycles.
Source & Purchase
For researchers requiring TIRZEPATIDE with full analytical documentation including HPLC and LC-MS traces, visit the PeptideSourceHub product page for bulk pricing and specifications.
Purchase TIRZEPATIDE with COA →
| Product |
Link |
| Semaglutide (GLP-1 RA) |
semaglutide.md — Selective GLP-1 receptor 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 |