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Molecular Weight
Purity
Storage
Appearance
Solubility
01
Mazdutide (development codes IBI362 and LY3305677) is a synthetic 34-residue peptide that activates two receptors: the GLP-1 receptor and the glucagon receptor. Its design started from oxyntomodulin, a natural gut hormone with weak activity at both receptors, and was extensively re-engineered for potency, stability and long duration of action.
A C20 fatty diacid attached to Lys20 enables albumin binding. With its GLP-1/glucagon profile, mazdutide fills a different position from the selective GLP-1 agonist semaglutide, the GIP/GLP-1 dual agonist tirzepatide and the GIP/GLP-1/glucagon triple agonist retatrutide. It is supplied as a lyophilized reference material for in vitro dual-receptor pharmacology and analytical work on lipidated peptides.
02
Mazdutide combines a glucagon/oxyntomodulin-like N-terminal region with features borrowed from other incretin analogues.
His1 and Aib2
The N-terminal histidine is shared with glucagon, GLP-1 and oxyntomodulin and is important for receptor activation. Aib at position 2 blocks DPP-IV cleavage.
Glucagon-like core
Residues such as Ser11, Lys12 and Tyr13 resemble glucagon and support glucagon receptor activity, while other substitutions tune the balance with GLP-1 receptor activity.
Lipidated Lys20
The side chain of Lys20 carries eicosanedioic acid (C20 diacid) linked through γ-glutamic acid and two AEEA units, the same type of side chain as tirzepatide. This is the albumin-binding element.
C-terminus
Unlike native oxyntomodulin, which ends in an eight-residue extension, mazdutide ends in Gly-Gly-Pro-Ser-Ser-Gly-NH₂, a short exendin-like sequence, with an amidated C-terminus.
Sensitive residues
Trp25 can photo-oxidise and Gln3 can deamidate; the many aspartate and glutamate residues make the peptide strongly acidic overall. There is no methionine or cysteine.
03
In vitro, mazdutide is characterised by measuring its activity at each target receptor separately.
Receptor binding
Published binding data report affinities in the tens-of-nanomolar range at both the human glucagon and GLP-1 receptors, giving a relatively balanced dual profile.
Functional activity
cAMP accumulation assays in GLP-1R- and GCGR-expressing cells give concentration–response curves at each receptor. As with all lipidated peptides, measured potency depends on albumin or serum content in the assay.
Glucagon receptor readouts
Beyond cAMP, glucagon receptor engagement in vitro is assessed in hepatocyte models through glucose output, glycogen breakdown and related signalling.
Comparative profiling
Run alongside semaglutide, tirzepatide and retatrutide to place it within the range of single, dual and triple agonists.
All observations described here come from cell-free and cell-based in vitro systems.
04
Dual GLP-1/glucagon reference
A reference compound for the GLP-1/glucagon co-agonist class in multi-receptor panels.
Lipidated peptide HPLC
Its C20 diacid side chain makes it a test compound for reversed-phase methods for acylated peptides, and a direct comparison to tirzepatide, which carries the same side chain on a different backbone.
Hepatocyte assays
Used to study glucagon receptor-driven responses in liver cell models alongside GLP-1 receptor-only comparators.
Forced degradation
Stress studies track Trp25 oxidation, deamidation, side-chain loss and backbone cleavage to build stability-indicating methods.
05
Storage
Store the lyophilized powder at −20 °C, sealed, desiccated and protected from light. Let the vial reach room temperature before opening.
Solubility
Reported as sparingly soluble in PBS at pH 7.2 (about 1–10 mg/mL). Some suppliers dissolve it in acidified water (around pH 2) for higher concentrations. Avoid intermediate pH values near its isoelectric point, where solubility is lowest.
Light sensitivity
Trp25 can photo-oxidise. Use amber or foil-wrapped containers.
Deamidation
Gln3 and other amide residues can deamidate slowly at neutral to basic pH. Freeze reconstituted aliquots and use them promptly.
Labware
Use low-binding polypropylene tubes and tips; the lipid promotes surface adsorption at low concentrations.
06
Analysis must confirm the redesigned backbone and the full lipid side chain.
HPLC
Wide-pore (300 Å) C4 or C8 columns at elevated temperature usually give the best peak shape and recovery. The des-lipid peptide is far less retained and separates easily; exact conditions are set during method development.
Mass spectrometry
ESI-MS shows multiply charged ions that deconvolute to about 4563.1 Da. Use formic acid rather than TFA for LC-MS.
Side-chain confirmation
Digestion followed by LC-MS/MS of the fragment containing Lys20 confirms the attachment site and the C20 diacid–γGlu–2×AEEA side chain.
Impurity profile
Typical checks include the des-lipid peptide, partially linked side chains, Trp25 oxidation (+16, +32 Da), deamidation (+1 Da), truncated sequences and the free-acid C-terminus.
07
Oxyntomodulin was the starting point: a natural 37-residue gut hormone that weakly activates both GLP-1 and glucagon receptors. Mazdutide is a heavily redesigned 34-residue version with Aib2, multiple substitutions, a C20 diacid side chain on Lys20 and an exendin-like C-terminus in place of oxyntomodulin’s eight-residue extension.
Both are lipidated GLP-1/glucagon receptor dual agonists, but they have different sequences, lipid side chains and molecular weights, and published data suggest different balances of activity between the two receptors. Mass spectrometry and peptide mapping readily tell them apart.
Mainly by cAMP accumulation in glucagon receptor-expressing cells, and in hepatocyte models by measuring glucose output and glycogen breakdown, compared against a GLP-1 receptor-only agonist such as semaglutide.
Because they are different molecules: their amino acid sequences, lengths and lipid side chains are not the same. Each compound’s molecular weight follows from its own composition rather than from its receptor profile.
Wide-pore (300 Å) C4 or C8 reversed-phase columns at elevated temperature are the usual starting point. They separate the des-lipid peptide easily; closely related species such as oxidised or deamidated forms need a shallow gradient optimised during method development.
It is sparingly soluble in PBS at pH 7.2 (about 1–10 mg/mL), which suits most in vitro work. For higher concentrations, some suppliers use acidified water. Avoid pH values near its isoelectric point, where solubility is lowest.
No. It is supplied strictly as a reference compound for laboratory and analytical research and is not for human or animal use.
Mazdutide Research Reference. (2026). Pure Peptides Labs Research Catalogue. Retrieved from https://purepeptideslabs.net/research-catalogue/metabolic-research-peptides/mazdutide/
Materials listed on this platform are supported by independent testing and published documentation for laboratory research contexts.
