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Tirzepatide | CAS: 2023788-19-2

CAS Number:
2023788-19-2
Chemical Classification:
Research peptide

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Laboratory programs investigating coordinated GIP and GLP-1 receptor biology frequently turn to tirzepatide, a 39-residue dual incretin agonist identified by CAS 2023788-19-2. The peptide's GIP-backbone architecture with C-terminal lipidation permits simultaneous engagement of pancreatic, adipose, and hypothalamic targets in a single exposure window—a design feature that distinguishes it from selective GLP-1 analogs in head-to-head pharmacology. Investigators adapt the compound to markedly different question sets: hepatic glucose-output perfusion, adipocyte lipid-partitioning models, and biased-agonism screens in heterologous receptor expression systems. Common bench applications involve nanomolar titration in cAMP accumulation assays, islet co-culture with alpha-cell glucagon readouts, and indirect calorimetry paired with controlled peptide infusion in rodent cohorts. Research-grade material ships with COA, LC-MS, HPLC, and NMR verification; not intended for clinical or therapeutic use.

CAS
2023788-19-2
Molecular Formula
C225H348N48O68
Molecular Weight
4813.5 g/mol
Purity
≥98%
Appearance
White to off-white lyophilized powder
Storage
Store at -20°C, desiccated

Analytical Documentation

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

Research Inquiry

Overview

Tirzepatide is a synthetic 39-amino-acid peptide engineered as a dual agonist of the glucose-dependent insulinotropic polypeptide receptor and the glucagon-like peptide-1 receptor. Its backbone derives from the native GIP sequence, with strategic amino acid substitutions and a C-terminal lipidation motif that extend receptor engagement and plasma residence in experimental systems. The molecule belongs to the incretin-mimetic class studied for coordinated regulation of postprandial glucose flux, pancreatic islet hormone secretion, and central-peripheral energy balance signaling. In laboratory models, tirzepatide serves as a pharmacological probe for dissecting how simultaneous GIPR and GLP-1R activation reshapes hepatic glucose output, adipocyte lipid handling, and hypothalamic satiety circuits compared with selective single-receptor agonists. Supplied at ≥98% purity (C225H348N48O68; 4813.5 g/mol), this material supports controlled laboratory investigation under research-use-only conditions.

Mechanism of Action

At the pathway level, tirzepatide activates GIPR and GLP-1R with balanced efficacy, triggering Gs-protein coupling and adenylyl cyclase elevation in beta cells, enteroendocrine L and K cells, and select neuronal populations. Downstream cAMP-PKA signaling augments glucose-stimulated insulin release while suppressing inappropriately timed glucagon secretion during hyperglycemic states. Parallel engagement of GIPR in adipose tissue modulates lipoprotein lipase activity and triglyceride partitioning, whereas GLP-1R signaling in the nucleus tractus solitarius influences autonomic outflow to the liver. Tirzepatide also slows gastric emptying through vagal and local enteric mechanisms, altering the rate of nutrient appearance in the portal circulation. These convergent pathways make the compound a useful tool for mapping incretin synergy in metabolic research platforms.

Receptor Binding & Signaling

Tirzepatide binds and activates human GIPR and GLP-1R with nanomolar potency in cell-based cAMP accumulation assays, exhibiting comparable maximal efficacy at both targets relative to native incretin peptides. Receptor selectivity profiling in heterologous expression systems indicates minimal cross-reactivity with glucagon receptor, amylin receptor complexes, or unrelated class B GPCRs at research-relevant concentrations. Lipidation facilitates albumin association, which modulates free peptide availability and receptor occupancy kinetics without altering intrinsic binding affinity at the orthosteric site. Biased signaling toward cAMP versus beta-arrestin recruitment has been characterized in some cell lines, informing how dual agonism translates to distinct transcriptional programs in islet and hypothalamic explants.

Research Applications

Incretin synergy and islet function

Researchers employ tirzepatide in isolated islet perifusion and static incubation models to compare dual GIPR-GLP-1R activation against selective agonists. The peptide enables quantification of first-phase insulin granule exocytosis, second-phase sustained release, and paracrine suppression of alpha-cell glucagon output under graded glucose concentrations. Patch-clamp and calcium-imaging workflows reveal how combined receptor signaling alters beta-cell electrical coupling and mitochondrial ATP production. These assays support structure-activity studies linking lipidation geometry and amino acid substitutions to receptor bias. Outcomes inform computational models of postprandial hormone dynamics without extrapolation to clinical endpoints.

Hepatic glucose production assays

In perfused liver and primary hepatocyte systems, tirzepatide is used indirectly through portal-mimetic hormone profiles or co-culture with islet organoids to evaluate suppression of gluconeogenic flux. Investigators measure PEPCK and G6Pase expression, glycogen phosphorylase activity, and tracer-based glucose output rates following peptide exposure. The dual incretin context allows separation of direct hepatic effects from indirect consequences of altered insulin and glucagon tone. Tirzepatide serves as a reference ligand in receptor-knockout backgrounds to attribute phenotypes to GIPR versus GLP-1R pathways. Such experiments advance understanding of inter-organ incretin communication in metabolic research.

Energy balance and adipose biology

Rodent and ex vivo adipose depot models utilize tirzepatide to probe GIPR-mediated lipid handling alongside GLP-1R-driven central appetite signaling. Researchers track adipocyte differentiation markers, mitochondrial respiration in inguinal versus visceral fat, and hypothalamic neuropeptide expression after controlled peptide administration in research protocols. Pairing tirzepatide with indirect calorimetry isolates effects on energy expenditure versus locomotor activity. The compound helps dissect whether adipose GIPR activation independently modifies thermogenesis or primarily acts through nutrient partitioning. These studies contribute to mechanistic maps of multi-receptor incretin biology.

Receptor pharmacology and bias profiling

Cell lines stably expressing human GIPR or GLP-1R are used for Bioluminescence Resonance Energy Transfer, internalization assays, and transcriptomic profiling after tirzepatide stimulation. Comparative head-to-head experiments with native GIP and GLP-1 clarify whether dual agonism produces additive, synergistic, or qualitatively distinct signaling fingerprints. Biased agonism metrics relate cAMP accumulation to beta-arrestin recruitment and ERK phosphorylation, supporting medicinal chemistry iterations on the tirzepatide scaffold. High-throughput screening platforms validate batch consistency of research material via EC50 and Emax reporting. This application domain emphasizes biophysical characterization rather than therapeutic outcome prediction.

Molecular Information

Sequence & Chain Summary

39-amino-acid peptide based on GIP backbone with C-terminal lipidation.

Modification Type

C20 fatty di-acid conjugation via gamma-Glu linker (similar to semaglutide lipidation strategy).

Structural Notes

Tirzepatide adopts an alpha-helical conformation characteristic of class B GPCR ligands, with the lipid moiety extending from the C terminus to promote albumin binding and reduce renal clearance in experimental pharmacokinetic studies. Alpha-amino isobutyric acid substitutions at positions 2 and 13 confer protease resistance relative to native GIP. The molecule's mass exceeds small-peptide thresholds, requiring LC-MS with high-resolution analyzers for identity confirmation. Circular dichroism in membrane-mimetic solvents supports helical stability across pH ranges relevant to formulation research. Batch-to-batch comparability relies on peptide mapping and free fatty acid content assays. Batch-specific molecular characterization—including mass confirmation and purity profiling—is available through COA, LC-MS, HPLC, and NMR documentation supplied with Tirzepatide.

Molecular Formula
C225H348N48O68
Molecular Weight
4813.5 g/mol
Purity Specification
≥98%

Experimental Notes

Stability

Lyophilized tirzepatide remains stable at −20°C for extended periods when protected from moisture and light. Reconstituted aqueous solutions show time-dependent aggregation at ambient temperature; aliquots should be frozen promptly after preparation. Repeated freeze-thaw cycles may reduce receptor activity in cell assays. Acidic to neutral pH preserves solubility in common research buffers. Certificate-of-analysis stability data should guide working solution shelf life in each laboratory. Lyophilized Tirzepatide 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. Tirzepatide is supplied as white to off-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 sterile research-grade water or dilute buffer compatible with downstream cell or tissue assays. Allow vials to equilibrate to room temperature before opening to minimize condensation. Use low-bind pipette tips when handling dilute peptide solutions to reduce surface adsorption. Document concentration by UV absorbance or quantitative LC-MS where available. Work under clean bench conditions and avoid prolonged exposure to strong oxidizers or extreme pH. 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 Tirzepatide. For laboratory use only — not medical advice.

What is Tirzepatide used for in research?
Tirzepatide is supplied for laboratory research investigating dual incretin receptor pharmacology, islet hormone secretion, and systemic metabolic signaling in controlled model systems. It is not intended for human or veterinary administration, diagnostic use, or food applications. Researchers should align protocols with institutional biosafety and chemical hygiene standards, using appropriate personal protective equipment and waste disposal routes. Material should be traceable via lot number and stored according to certificate-of-analysis guidance.
How does Tirzepatide work biologically?
Tirzepatide simultaneously activates GIP and GLP-1 receptors, elevating cAMP in responsive cells and coordinating insulin release, glucagon suppression, and gastric motility changes in research models. Dual engagement distinguishes its signaling profile from selective GLP-1 agonists in comparative experiments.
What receptors does Tirzepatide interact with?
Primary targets are the GIP receptor (GIPR) and GLP-1 receptor (GLP-1R), both class B GPCRs coupled predominantly to Gs. Off-target screening at research concentrations typically excludes meaningful activation of glucagon receptor or unrelated peptide hormone receptors.
Is Tirzepatide stable at room temperature?
Lyophilized tirzepatide remains stable at −20°C for extended periods when protected from moisture and light. Reconstituted aqueous solutions show time-dependent aggregation at ambient temperature; aliquots should be frozen promptly after preparation. Repeated freeze-thaw cycles may reduce receptor activity in cell assays. Acidic to neutral pH preserves solubility in common research buffers. Certificate-of-analysis stability data should guide working solution shelf life in each laboratory. For short-term laboratory workflows, minimize time at room temperature and return unused material to recommended storage promptly. Tirzepatide is not formulated for ambient long-term storage.
What is the recommended storage condition for Tirzepatide?
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.