Compound monograph
Mazdutide
Mazdutide is a lipidated synthetic peptide classified as a GLP-1 and glucagon receptor dual agonist, built on an oxyntomodulin-derived backbone.
01
Identity & nomenclature
Mazdutide is a lipidated synthetic peptide classified as a GLP-1 and glucagon receptor dual agonist, built on an oxyntomodulin-derived backbone.
The formula recorded here is the WHO-defined structure. PubChem's name-linked record reports C207H317N45O65, which differs by exactly one serine residue — C3H5NO2, 87.0320 Da. That is a difference in covalent peptide composition, not a salt form or a protonation state. This library anchors identity to the WHO 34-residue structure ending GGPSSG-NH2 and records no PubChem CID until the disagreement is reconciled upstream. The discrepancy is evidence of a database conflict; it is not evidence about what any particular sample contains.
Declared aliases and development codes: IBI362, IBI-362, LY3305677, LY-3305677, IBI362, LY3305677.
02
Molecular properties
| Molecular formula | C210H322N46O67 |
|---|---|
| Molecular mass | 4563.07 Da |
| CAS Registry Number | 2259884-03-0 |
| UNII | MB76Z4IBZ5 |
| Three-letter sequence | His–Aib–Gln–Gly–Thr–Phe–Thr–Ser–Asp–Tyr–Ser–Lys–Tyr–Leu–Asp–Glu–Lys–Lys–Ala–Lys–Glu–Phe–Val–Glu–Trp–Leu–Leu–Glu–Gly–Gly–Pro–Ser–Ser–Gly–NH2 |
Thirty-four residues ending Gly-Gly-Pro-Ser-Ser-Gly with a C-terminal amide. BOTH serines near the C-terminus belong in the sequence; a species missing one would be 87.0320 Da lighter. Position 2 is Aib, 2-aminoisobutyric acid — not Ac4c, which is what survodutide carries. Lys20 is acylated through two AEEA spacers, a gamma-L-glutamyl unit and a C20 dicarboxylic fatty acid.
03
Structural characteristics
Described in its literature as an oxyntomodulin analog. Oxyntomodulin contains the complete glucagon sequence plus the eight-residue extension KRNRNNIA, so mazdutide's backbone belongs to the glucagon family at its N-terminal end while its engineered C-terminal segment replaces that native extension. The related oxyntomodulin entry identifies the stated structural parent; the glucagon relationship is inherited through oxyntomodulin, rather than a claim of direct glucagon ancestry. GLP-1(7-36) amide is a native receptor comparator, not a structural parent. Position 2 is alpha-aminoisobutyric acid, not the Ac4c of survodutide, and lipidation uses two AEEA spacers from the lysine 20 side chain. Survodutide and mazdutide share a receptor profile and are not chemically interchangeable. The dual-receptor classification is supported at the target-class level. What is NOT established in the verified source set, and is stated here rather than filled in: a quantitative receptor potency ratio for this compound, matched binding affinities, full-versus-partial agonist classification under defined conditions, and signalling-bias parameters. Every reference in this entry is Class B — none is a mazdutide-bound structure or a mazdutide-specific receptor pharmacology study. Findings from comparator dual agonists describe those comparators. Being oxyntomodulin-derived is not permission to substitute oxyntomodulin's sequence or another dual agonist's data.
- Aib at position 2
- Lys20 acylation via two AEEA spacers and gamma-Glu
- C20 dicarboxylic fatty-acid acylation
Terminal features: Free N-terminus, C-terminal amide at Gly34.
04
Molecular targets & mechanisms
Glucagon-like peptide-1 receptor
GLP-1R
GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.
Glucagon receptor
GCGR
GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.
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Analytical considerations
The first identity question is whether a sample matches the WHO-defined composition rather than the mass attached to a name-matched database record. Tandem MS should establish the C-terminal Pro-Ser-Ser-Gly segment and verify both serines independently; a species short one serine is 87.0320 Da lighter, which intact mass can flag but only fragmentation can localise. The remaining features are Aib2, Lys20 conjugation, TWO AEEA spacers, gamma-Glu connectivity, the C20 diacid and the Gly34 amide. A correct intact mass without branch mapping does not exclude a linker-connectivity isomer. A certificate reporting only HPLC purity and an approximate 4.5 kDa mass does not resolve the database conflict above.
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Verified bibliography
- Structural analysis of the dual agonism at GLP-1R and GCGR.current
Li Y, Zhou Q, Dai A, Zhao F, Chang R, Ying T, Wu B, Yang D, Wang MW, Cong Z
Proceedings of the National Academy of Sciences of the United States of America · 2023-08-07 · Journal Article
- Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors.current
Darbalaei S, Yuliantie E, Dai A, Chang R, Zhao P, Yang D, Wang MW, Sexton PM, Wootten D
Biochemical pharmacology · 2020-07-17 · Journal Article
- Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.current
Pickford P, Lucey M, Rujan RM, McGlone ER, Bitsi S, Ashford FB, Corrêa IR, Hodson DJ, Tomas A, Deganutti G, Reynolds CA, Owen BM, Tan TM, Minnion J, Jones B, Bloom SR
Molecular metabolism · 2021-04-30 · Journal Article
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Methodology & citation verification
Reference identity is checked against official PubMed metadata. Local deterministic receipts bind each normalized title and canonical metadata record to its verification date. Scientific values remain absent when an authoritative source has not been verified.
Read the full methodology →