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.
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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.
Declared aliases and development codes: NN9535, NNC 0113-0217.
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Molecular properties
| Molecular formula | C187H291N45O59 |
|---|---|
| Molecular mass | 4114 Da |
| CAS Registry Number | 910463-68-2 |
| PubChem CID | 56843331 |
| UNII | 53AXN4NNHX |
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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
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Molecular targets & mechanisms
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Analytical considerations
Identity assessment must account for both the peptide sequence and the Lys26-linked side chain represented in the PubChem molecular record.
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Verified bibliography
- Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide.current
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
- Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes.current
Zhang X, Belousoff MJ, Liang YL, Danev R, Sexton PM, Wootten D
Cell reports · 2021-07-13 · Journal Article
- The Discovery and Development of Liraglutide and Semaglutide.current
Knudsen LB, Lau J
Frontiers in endocrinology · 2019-04-12 · Review
- Semaglutide lowers body weight in rodents via distributed neural pathways.current
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
- Pharmacology, physiology, and mechanisms of incretin hormone action.current
Campbell JE, Drucker DJ
Cell metabolism · 2013-05-16 · Review
- Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.current
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
- Structural basis for ligand recognition of incretin receptors.current
Underwood CR, Parthier C, Reedtz-Runge S
Vitamins and hormones · 2010 · Review
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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.
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