Compound monograph
Semaglutide
Semaglutide is an acylated peptide analog of glucagon-like peptide-1. Its discovery record identifies two amino-acid substitutions and derivatization at Lys26.
01
Identity & nomenclature
Semaglutide is an acylated peptide analog of glucagon-like peptide-1. Its discovery record identifies two amino-acid substitutions and derivatization at Lys26.
PubChem lists NN9535 and NNC 0113-0217 as development identifiers for the semaglutide molecular record. WHO Proposed INN List 101 and Recommended List 63 print position 8 in English as 2-amino-2-propanoic acid, without the methyl that their French and Spanish names include; this record keeps Aib, 2-aminoisobutyric acid.
Declared aliases and development codes: NN9535, NNC 0113-0217.
02
Molecular properties
| Molecular formula | C187H291N45O59 |
|---|---|
| Molecular mass | 4114 Da |
| CAS Registry Number | 910463-68-2 |
| PubChem CID | 56843331 |
| UNII | 53AXN4NNHX |
| Three-letter sequence | His–Aib–Glu–Gly–Thr–Phe–Thr–Ser–Asp–Val–Ser–Ser–Tyr–Leu–Glu–Gly–Gln–Ala–Ala–Lys–Glu–Phe–Ile–Ala–Trp–Leu–Val–Arg–Gly–Arg–Gly |
| Terminal groups | Free N-terminus; Free C-terminal carboxyl |
Thirty-one residues in the conventional GLP-1 7-37 numbering this library keeps for every analog built on that scaffold: the first token is His7 and the last is Gly37, so a position number in this entry is the array index plus six, and Lys26 is the twentieth token. NO one-letter string is published here. Position 8 is Aib, 2-aminoisobutyric acid; written as Ala it would name the native residue this analog exists to replace, and any other letter would name a different amino acid again. The IUPHAR/BPS Guide to Pharmacology (ligand 9724, release 2026.3.1) prints Ala at position 8 in its sequence fields while its structure encodes Aib; FDA GSRS also records Aib there. The backbone is also not the whole molecule: the Lys26 side chain is acylated through two AEEA spacers and a gamma-L-glutamyl unit to a C18 dicarboxylic fatty acid. Summing the thirty-one residues with Aib at position 8 and Arg at position 34, removing thirty waters, then adding two AEEA units, one glutamyl unit and octadecanedioic acid less the four waters of the four amide bonds, gives C187H291N45O59 and an average mass of 4113.64 Da, reproducing the recorded formula exactly and the recorded mass to 0.36 Da. Against the machine-verified GLP-1(7-37) entry that backbone differs by exactly CH2 and N2 — the Aib8 and Arg34 substitutions, and nothing else. That arithmetic is the identity check this record rests on; the automated sequence verifier cannot reach it, because Aib and the acyl side chain are both outside its derivation model.
03
Structural characteristics
Built on the GLP-1(7-37) scaffold, retaining its C-terminal glycine. Using native GLP-1 numbering, it carries alpha-aminoisobutyric acid at position 8 in place of alanine, arginine at position 34 in place of lysine, and acylation of the lysine 26 side chain through a gamma-glutamyl unit and two AEEA spacers to a C18 fatty diacid. The position-8 substitution sits at the dipeptidyl peptidase IV cleavage site described on the native GLP-1 entries; resistance to that cleavage is the stated design rationale, not independent causal proof for each substitution. The related GLP-1(7-37) entry identifies the native structural parent. The Aib8 and Arg34 substitutions distinguish the peptide backbone from human GLP-1, while the Lys26-linked side chain is part of the declared molecular identity.
- Aib substitution at position 8
- Arg substitution at position 34
- Lys26 derivatization with a fatty-diacid-containing side chain
Terminal features: Free N-terminus, Free C-terminal carboxyl.
04
Molecular targets & mechanisms
05
Analytical considerations
Identity assessment must account for both the peptide sequence and the Lys26-linked side chain represented in the PubChem molecular record.
Disagreements and mix-ups
Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.
Sources disagree · this Library follows one source · Notation
How semaglutide's position-8 residue is written
What the studies reported
Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.
Cell and tissue studies
GLP-1 receptor affinity assay
Lau et al. measured a semaglutide GLP-1 receptor affinity of 0.38 ± 0.06 nM in an in-vitro receptor affinity assay.
Reference [1]GLP-1R–Gs protein complexes
Zhang et al. reported cryo-EM structures and identified receptor and bound-peptide motions in semaglutide-bound GLP-1R–Gs protein complexes in vitro.
Reference [2]
Animal studies
Mini-pigs
Lau et al. measured a semaglutide plasma half-life of 46.1 h in mini-pigs.
Reference [1]Mini-pigs
Lau et al. measured a semaglutide mean residence time of 63.6 h in mini-pigs.
Reference [1]Rat area postrema tissue
Gabery et al. observed upregulation of prolactin-releasing hormone and tyrosine hydroxylase in microdissected area postrema tissue from rats exposed to semaglutide.
Reference [4]
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Verified bibliography
Cited studies by type
The 7 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.
A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.
Reference 1
Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide.Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T
Journal of medicinal chemistry · 2015-09-11 · Journal Article
currentReference 2
Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes.Zhang X, Belousoff MJ, Liang YL, Danev R, Sexton PM, Wootten D
Cell reports · 2021-07-13 · Journal Article
currentReference 3
The Discovery and Development of Liraglutide and Semaglutide.Knudsen LB, Lau J
Frontiers in endocrinology · 2019-04-12 · Review
currentReference 4
Semaglutide lowers body weight in rodents via distributed neural pathways.Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF, Buckley ST, Farkas E, Fekete C, Frederiksen KS, Helms HCC, Jeppesen JF, John LM, Pyke C, Nøhr J, Lu TT, Polex-Wolf J, Prevot V, Raun K, Simonsen L, Sun G, Szilvásy-Szabó A, Willenbrock H, Secher A, Knudsen LB, Hogendorf WFJ
JCI insight · 2020-03-26 · Journal Article
currentReference 5
Pharmacology, physiology, and mechanisms of incretin hormone action.Campbell JE, Drucker DJ
Cell metabolism · 2013-05-16 · Review
currentReference 6
Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G
Nature · 2017-05-24 · Journal Article
currentReference 7
Structural basis for ligand recognition of incretin receptors.Underwood CR, Parthier C, Reedtz-Runge S
Vitamins and hormones · 2010 · Review
current
Study models of these references
What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.
| Reference | Study models |
|---|---|
| Lau J et al. 2015 | Study models reported: in vitro; animal (mini-pig) · from the abstract |
| Zhang X et al. 2021 | Study models reported: in vitro · from the abstract |
| Knudsen LB et al. 2019 | Review article |
| Gabery S et al. 2020 | Study models reported: in vitro; animal (rat, mouse) · from the full text |
| Campbell JE et al. 2013 | Review article |
| Zhang Y et al. 2017 | Study models reported: in vitro · from the abstract |
| Underwood CR et al. 2010 | Review article |
Compare
Record history
Published 2026-09-04.
- : Identity and nomenclature, Sequence and structure
- : Sequence and structure
- : Sequence and structure
- : References
Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.
Cite this record: Purely Peptides Research Library. Semaglutide. Published 2026-09-04; updated 2026-10-12. https://purelypeptides.org/research/compounds/semaglutide/
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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 →