Compound monograph
Glucagon
Glucagon is the endogenous 29-residue pancreatic hormone and the native ligand of the glucagon receptor.
01
Identity & nomenclature
Glucagon is the endogenous 29-residue pancreatic hormone and the native ligand of the glucagon receptor.
Mature glucagon, not proglucagon and not a generic glucagon-family peptide. Glucagon, GLP-1 and oxyntomodulin are related through processing of a shared precursor but are not aliases. Note particularly that this entire 29-residue sequence is contained within oxyntomodulin, which extends it by eight residues — that containment is exactly why the two are analytically difficult to separate.
Declared aliases and development codes: Glucagon(1-29).
02
Molecular properties
| Molecular formula | C153H225N43O49S |
|---|---|
| Molecular mass | 3482.8 Da |
| CAS Registry Number | 16941-32-5 |
| UNII | 76LA80IG2G |
| One-letter sequence | HSQGTFTSDYSKYLDSRRAQDFVQWLMNT |
Twenty-nine residues, free at both termini, no modifications.
03
Structural characteristics
Cryo-electron microscopy structures of glucagon bound to the human glucagon receptor in complex with two different heterotrimeric G proteins establish exact-hormone receptor recognition, with conformational differences in the receptor intracellular loops identified as selectivity determinants and supported by mutagenesis. Being an agonist at this receptor does not, in the other direction, establish a glucagon-derived backbone: compounds in this library activate the glucagon receptor from scaffolds that are not glucagon-derived at all.
04
Molecular targets & mechanisms
05
Analytical considerations
A shared glucagon-region epitope or internal sequence is insufficient to discriminate glucagon from larger proglucagon-derived peptides that contain it in full. Identity work should target intact-molecule specificity and calibrant identity rather than assuming all glucagon-reactive material is mature glucagon. A validated mass-spectrometric method separating glucagon from oxyntomodulin exists and is the appropriate reference point for that problem.
06
Verified bibliography
- Structural basis of G(s) and G(i) recognition by the human glucagon receptor.current
Qiao A, Han S, Li X, Li Z, Zhao P, Dai A, Chang R, Tai L, Tan Q, Chu X, Ma L, Thorsen TS, Reedtz-Runge S, Yang D, Wang MW, Sexton PM, Wootten D, Sun F, Zhao Q, Wu B
Science (New York, N.Y.) · 2020-03-20 · 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
- 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
10
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 →