Compound monograph
Oxyntomodulin
Oxyntomodulin is an endogenous proglucagon-derived peptide containing the complete glucagon sequence plus an eight-residue C-terminal extension, with reported activity at both the GLP-1 and glucagon receptors.
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Identity & nomenclature
Oxyntomodulin is an endogenous proglucagon-derived peptide containing the complete glucagon sequence plus an eight-residue C-terminal extension, with reported activity at both the GLP-1 and glucagon receptors.
Oxyntomodulin is ONE peptide, not a mixture of GLP-1 and glucagon. It is also not glicentin, which is a larger processing product that contains the oxyntomodulin region — and both carry the same KRNRNNIA C-terminus, so recognising that region does not distinguish them. Separately, 'oxyntomodulin-like' is a description of GLP-1R/GCGR pharmacology and does not establish oxyntomodulin-derived chemistry; a compound can have that pharmacology from a different scaffold entirely. FINALLY, AND THE REASON NO pubChemCid IS RECORDED: PubChem CID 16144019 displays the C-terminus as KRNKNNIA, with lysine where the reviewed human sequence has arginine at oxyntomodulin position 33. Arginine carries two more nitrogens than lysine, which is why that record shows N59 against this entry's N61. Its formula and mass describe a variant and must not be applied to the human sequence.
Declared aliases and development codes: OXM, Glucagon-37.
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Molecular properties
| Molecular formula | C192H295N61O60S |
|---|---|
| Molecular mass | 4449.9 Da |
| UNII | LV7ELH7V16 |
| One-letter sequence | HSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIA |
Thirty-seven residues, free at both termini. The first twenty-nine are the complete glucagon sequence; the C-terminal extension is KRNRNNIA. Species and the extension must both be explicit.
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Structural characteristics
Its dual-receptor character was dissected using a single-residue variant: replacing glutamine with glutamate at position 3 retained comparable potency at the murine GLP-1 receptor while removing significant murine glucagon-receptor agonist activity in vitro and reducing the ability to stimulate glycogenolysis in perfused mouse liver by roughly one hundred-fold. These receptor and liver assays distinguish the GLP-1R and GCGR components of oxyntomodulin signaling. The library cites that work for this receptor dissection specifically. There is no separate established oxyntomodulin receptor to name; the mechanism is the two receptors it shares with other proglucagon-derived peptides.
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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
Identity work must discriminate oxyntomodulin from BOTH glucagon and glicentin. An internal glucagon-derived segment cannot identify it uniquely, because glucagon's entire sequence is contained within it. A C-terminal antibody does not solve this either: antisera raised against the KRNRNNIA extension cross-react completely with both oxyntomodulin and glicentin while showing none toward glucagon. Chromatographic or mass-spectrometric separation is therefore the appropriate approach, and a validated LC-MS/MS method distinguishing oxyntomodulin from glucagon exists.
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Verified bibliography
- Development of an oxyntomodulin/glicentin C-terminal radioimmunoassay using a "thiol-maleoyl" coupling method for preparing the immunogen.current
Blache P, Kervran A, Martinez J, Bataille D
Analytical biochemistry · 1988-08-15 · Journal Article
- Quantification of glucagon and oxyntomodulin by protein precipitation-immunoaffinity enrichment-LC-MS/MS.current
Becker JO, Shijo SK, Huynh HH, Forrest KL, MacCoss MJ, Emrick MA, Goonatilleke E, Hoofnagle AN
Journal of mass spectrometry and advances in the clinical lab · 2025-04-11 · Journal Article
- The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.current
Kosinski JR, Hubert J, Carrington PE, Chicchi GG, Mu J, Miller C, Cao J, Bianchi E, Pessi A, Sinharoy R, Marsh DJ, Pocai A
Obesity (Silver Spring, Md.) · 2012-03-16 · Journal Article
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Methodology & citation verification
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