Compound monograph
Tirzepatide
Tirzepatide is a fatty-acid-modified synthetic peptide characterized in its discovery record as having agonist activity at both the GIP receptor and the GLP-1 receptor.
01
Identity & nomenclature
Tirzepatide is a fatty-acid-modified synthetic peptide characterized in its discovery record as having agonist activity at both the GIP receptor and the GLP-1 receptor.
The discovery record identifies the molecule under the development code LY3298176. GSRS UNII OYN3CCI6QE identifies the specified tirzepatide sequence and modifications and lists CAS 2023788-19-2, although its retrieved codes do not include PubChem CID 166567236.
Declared aliases and development codes: LY3298176.
02
Molecular properties
| Molecular formula | C225H348N48O68 |
|---|---|
| Molecular mass | 4813 Da |
| CAS Registry Number | 2023788-19-2 |
| PubChem CID | 166567236 |
| UNII | OYN3CCI6QE |
| Three-letter sequence | Tyr–Aib–Glu–Gly–Thr–Phe–Thr–Ser–Asp–Tyr–Ser–Ile–Aib–Leu–Asp–Lys–Ile–Ala–Gln–Lys–Ala–Phe–Val–Gln–Trp–Leu–Ile–Ala–Gly–Gly–Pro–Ser–Ser–Gly–Ala–Pro–Pro–Pro–Ser |
| Terminal groups | Free N-terminus; C-terminal amide at Ser39 |
Thirty-nine residues numbered from the N-terminus; the C-terminal amide on Ser39 is recorded as a terminal group, not as a residue. NO one-letter string is published here: positions 2 and 13 are both Aib, 2-aminoisobutyric acid, and no standard letter names that residue. Residue 1 is Tyr, the GIP N-terminus rather than GLP-1's His. There are two lysines, at 16 and 20, and the acylation site is Lys20. The backbone is not the whole molecule: that Lys20 side chain is acylated through two AEEA spacers and a gamma-L-glutamyl unit to a C20 dicarboxylic fatty acid. Summing the thirty-nine residues with Aib at 2 and 13, removing thirty-eight waters, applying the Ser39 amide, then adding two AEEA units, one glutamyl unit and eicosanedioic acid less the four waters of the four amide bonds, gives C225H348N48O68, reproducing the recorded formula exactly; the derived average mass is 4813.53 Da against a recorded 4813, which is a truncation of that value rather than a rounding of it. Residues 29 to 39 are Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser; that tail is shared with other 39-residue incretin peptides and is not by itself evidence of ancestry, which the structural notes take up. 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 outside its derivation model.
03
Structural characteristics
The scaffold is GIP, not GLP-1. Residue 1 is tyrosine, matching GIP's N-terminal Tyr-Ala rather than GLP-1's His-Ala, and across residues 1-29 it is closer to GIP than to GLP-1. Relative to human GIP it carries alpha-aminoisobutyric acid at positions 2 and 13, and substitutions at positions 7, 14, 18, 20, 21, 24, 27 and 29; the native GIP C-terminal segment is replaced by a shorter engineered tail with a C-terminal amide, and the lysine 20 side chain carries a C20 fatty diacid. The related GIP(1-42) entry identifies scaffold ancestry; GLP-1(7-36) amide is a native receptor comparator. Activity at the GLP-1 receptor is a pharmacological property of the engineered molecule and does not establish GLP-1 ancestry. The discovery record describes tirzepatide as a fatty acid modified peptide with activity at both incretin receptors. Receptor-level characterization reports greater engagement at the GIP receptor than at the GLP-1 receptor, and at the GLP-1 receptor a signaling profile favoring cAMP generation over beta-arrestin recruitment, with weaker GLP-1 receptor internalization than GLP-1 itself.
- Fatty-acid moiety linked to the peptide backbone
Terminal features: Free N-terminus, C-terminal amide at Ser39.
04
Molecular targets & mechanisms
Glucose-dependent insulinotropic polypeptide receptor
GIPR
GIPR is a class B G-protein-coupled receptor. The cited discovery and trial records identify it as one of the three receptor relationships declared for retatrutide.
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.
05
Analytical considerations
Identity assessment must account for both the peptide backbone and the fatty-acid modification represented in the PubChem molecular record. PubChem CID 166567236 is retained because it encodes the specified peptide stereochemistry and gamma-L-glutamyl lipid linker, whereas the other four name-linked CIDs contain stereochemical substitutions or undefined centres. GSRS UNII OYN3CCI6QE matches the sequence and structural modifications but reports C225H347N49O66, conflicting with this record and PubChem CID 166567236 at C225H348N48O68.
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
Cell lines expressing recombinant or endogenous incretin receptors
Coskun et al. observed activation of both GIP and GLP-1 receptor signaling by LY3298176 in in-vitro cell-line assays expressing recombinant or endogenous incretin receptors.
Reference [1]GLP-1 receptor signaling assays
Willard et al. observed tirzepatide signaling biased toward cAMP generation over β-arrestin recruitment at the GLP-1 receptor in in-vitro signaling assays.
Reference [2]
Animal studies
Mice
Coskun et al. observed glucose-dependent insulin secretion and improved glucose tolerance through both GIP and GLP-1 receptors in mice exposed to LY3298176.
Reference [1]
06
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
LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A
Molecular metabolism · 2018-10-03 · Journal Article
currentReference 2
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ, Holst JJ, D'Alessio DA, Coghlan MP, Rosenkilde MM, Campbell JE, Sloop KW
JCI insight · 2020-09-03 · Journal Article
currentReference 3
Pharmacology, physiology, and mechanisms of incretin hormone action.Campbell JE, Drucker DJ
Cell metabolism · 2013-05-16 · Review
currentReference 4
How May GIP Enhance the Therapeutic Efficacy of GLP-1?Samms RJ, Coghlan MP, Sloop KW
Trends in endocrinology and metabolism: TEM · 2020-03-16 · Review
currentReference 5
Structural determinants of dual incretin receptor agonism by tirzepatide.Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW
Proceedings of the National Academy of Sciences of the United States of America · 2022-03-25 · Journal Article
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 |
|---|---|
| Coskun T et al. 2018 | Study models reported: in vitro; animal (mouse); human participants (interventional) · from the abstract |
| Willard FS et al. 2020 | Study models reported: in vitro · from the full text |
| Campbell JE et al. 2013 | Review article |
| Samms RJ et al. 2020 | Review article |
| Sun B et al. 2022 | Study models reported: in vitro · from the abstract |
| 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.
- : Sequence and structure
- : Identity and nomenclature, Analytical notes
- : 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. Tirzepatide. Published 2026-09-04; updated 2026-10-15. https://purelypeptides.org/research/compounds/tirzepatide/
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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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