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. PubChem lists no UNII for this record, so no UNII is published here.
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 |
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
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.
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Analytical considerations
Identity assessment must account for both the peptide backbone and the fatty-acid modification represented in the PubChem molecular record.
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Verified bibliography
- 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.current
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
- Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.current
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
- Pharmacology, physiology, and mechanisms of incretin hormone action.current
Campbell JE, Drucker DJ
Cell metabolism · 2013-05-16 · Review
- How May GIP Enhance the Therapeutic Efficacy of GLP-1?current
Samms RJ, Coghlan MP, Sloop KW
Trends in endocrinology and metabolism: TEM · 2020-03-16 · Review
- Structural determinants of dual incretin receptor agonism by tirzepatide.current
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
- 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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