Compound monograph
Survodutide
Survodutide is a lipidated synthetic peptide agonist at both the GLP-1 receptor and the glucagon receptor, built on a modified glucagon-family backbone with a branched side-chain linker.
01
Identity & nomenclature
Survodutide is a lipidated synthetic peptide agonist at both the GLP-1 receptor and the glucagon receptor, built on a modified glucagon-family backbone with a branched side-chain linker.
A registry representation showing the main chain and the linker as separate sequences does not mean the substance is a mixture of two peptides. Survodutide and mazdutide are both GLP-1/glucagon dual agonists and are not interchangeable: they differ in main-chain sequence, nonstandard residue, conjugation position, linker and lipid. Shared receptor pharmacology is a classification, not chemical equivalence.
Declared aliases and development codes: BI 456906, BI-456906, BI 456906.
02
Molecular properties
| Molecular formula | C192H289N47O61 |
|---|---|
| Molecular mass | 4231.63 Da |
| CAS Registry Number | 2805997-46-8 |
| PubChem CID | 171378821 |
| UNII | 2ALA66NS64 |
| Three-letter sequence | His–Ac4c–Gln–Gly–Thr–Phe–Thr–Ser–Asp–Tyr–Ser–Lys–Tyr–Leu–Asp–Glu–Arg–Ala–Ala–Lys–Asp–Phe–Ile–Lys–Trp–Leu–Glu–Ser–Ala–NH2 |
Position 2 is Ac4c, 1-aminocyclobutane-1-carboxylic acid. It is NOT Aib. The two differ by one carbon, 12.0000 Da exactly, and substituting one for the other imports the chemistry of a different peptide. The 29-residue main chain is also not the whole molecule: a gamma-Glu-Gly-Ser-Gly-Ser-Gly-Gly linker is amidated to the Lys24 side chain and carries a C18 dicarboxylic fatty acid.
03
Structural characteristics
The 29-residue main chain is glucagon-derived. Position 2 carries 1-aminocyclobutane-1-carboxylic acid (Ac4c), not the alpha-aminoisobutyric acid found in several other analogs here, with further substitutions along the chain, a C-terminal amide, and a branched linker from the lysine 24 side chain to a C18 fatty diacid. The related glucagon entry identifies scaffold ancestry; GLP-1(7-36) amide is a native receptor comparator. GLP-1 receptor activity is engineered and does not indicate GLP-1 ancestry. Survodutide is not oxyntomodulin-derived; that description belongs to mazdutide. Functional potencies at the two receptors have been reported in a single cAMP assay system containing bovine serum albumin. Those are assay-specific functional values, not equilibrium binding affinities, and protein content in the assay materially affects the apparent profile. The published values should not be restated as an invariant balanced ratio, and a full-versus-partial agonist classification independent of assay conditions is not established.
- Ac4c at position 2
- Lys24 side-chain branched linker
- C18 dicarboxylic fatty-acid acylation
Terminal features: Free N-terminus, C-terminal amide at Ala29.
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
Confirmation requires the intact mass, the 29-residue main chain, Ac4c at position 2, conjugation at Lys24, the complete linker, the C18 diacid and the Ala29 amide. Tandem MS coverage is needed on both sides of Lys24; a backbone-only database match does not characterise the branch. A GLP-1R and GCGR cAMP panel confirms a functional profile, not molecular identity, because other dual agonists produce similar responses. For bulk powder, counterion, water and peptide content are separate measurements from chromatographic area purity.
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Verified bibliography
- BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.current
Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ, Klein H, Santhanam R, Hamprecht D, Neubauer H, Augustin R
Molecular metabolism · 2022-11-07 · Journal Article
- The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.current
Thomas L, Martel E, Rist W, Uphues I, Hamprecht D, Neubauer H, Augustin R
Diabetes, obesity & metabolism · 2024-04-01 · Journal Article
- 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
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Methodology & citation verification
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