Research Library › Articles · View in catalog →
Tirzepatide
Also indexed as Tirzepatide (INN), LY3298176, CAS 2023788-19-2
1 Identity
Acylated synthetic lipopeptide, not a plain peptide. A 39-residue single-chain backbone of GIP-analog design, C-terminally amidated, carrying two 2-aminoisobutyric acid substitutions, with a C20 fatty diacid conjugated to a lysine side chain through a gamma-glutamate spacer and two AEEA units. Four structural features that a residue count conceals and that a plain-peptide specification is blind to: Aib at positions 2 and 13; the C-terminal amide; the acylation itself; and the position of the acylation, since the chain carries a second, unmodified lysine. Contained in the FDA-approved drug products Mounjaro and Zepbound (NDA 217806), both Eli Lilly. Gray-market shorthand is recorded here so the regulatory watch can recognize listings, and is used nowhere in this company's records, certificates, labels or invoices: "twincretin", "MHC-2 TRZ".
- Sequence
- Tyr1-Aib2-Glu3-Gly4-Thr5-Phe6-Thr7-Ser8-Asp9-Tyr10-Ser11-Ile12-Aib13-Leu14-Asp15-Lys16-Ile17-Ala18-Gln19-Lys20-Ala21-Phe22-Val23-Gln24-Trp25-Leu26-Ile27-Ala28-Gly29-Gly30-Pro31-Ser32-Ser33-Gly34-Ala35-Pro36-Pro37-Pro38-Ser39-NH2, with the Lys20 side-chain N-epsilon bearing (AEEA)-(AEEA)-(gamma-Glu)-(C20 diacid), written out as Lys20(epsilon)-NH-[AEEA-AEEA-gamma-Glu-CO(CH2)18COOH]. Two AEEA units, not one; that is the feature that separates this molecule's linker from retatrutide's. Aib at positions 2 and 13 only. Lys16 is present and unmodified, and that is the positional-isomer risk. Thirty-nine residues, no disulfides. Supplied commercially as the acetate salt.
- Molecular formula
- C225H348N48O68 (free base). Des-acyl 39-mer backbone C188H283N45O56. The acyl side chain contributes C37H65N3O12 net, after replacing one hydrogen on the lysine epsilon-amine.
- Average mass
- Average mass 4813.527 Da (C225H348N48O68), computed from the formula. The FDA-approved Zepbound labeling, revision 02/2026, states the same formula and a molecular weight of 4813.53 Da. That is 0.003 Da from the figure above, or 0.6 ppm at 4.8 kDa. Des-acyl backbone 4069.591 Da, giving a des-acylation interval of 743.936 Da average. Mono-acetate salt 4873.579 Da.
- Monoisotopic mass
- 4810.52486 Da neutral (C225H348N48O68); [M+H]+ 4811.53213. At this mass the measurement that matters is the deconvoluted multiply-charged envelope, and identity work requires not less than 30,000 resolving power, because the C-terminal amide versus free acid difference is 0.984 Da and is invisible below that. Des-acyl backbone 4067.06803, giving a des-acylation interval of 743.4568 Da monoisotopic.
- Salt / variant note
- All figures computed on the IUPAC 2021 abridged table. Wrong-molecule substitutions, each separable by arithmetic on one calculator: semaglutide C187H291N45O59, 4113.641 / 4111.11538, 699.886 Da lighter, the cheaper API, the same colorless cake, and the single most documented substitution in this channel, so a certificate showing about 4113 is not this article; retatrutide C221H342N46O68, 4731.421 / 4728.47176, only 82.106 Da away, 1.7 percent at 4.8 kDa, which a nominal-mass MALDI trace with a broad peak will not cleanly separate; liraglutide C172H265N43O51, 3751.262 / 3748.94646. Within-molecule variants, each checkable against the supplier's own declared parent mass with no reference standard in hand. Des-acyl tirzepatide, the bare 39-mer carrying both Aib substitutions and the C-terminal amide but no side chain, C188H283N45O56, 4069.591 / 4067.06803, an interval of 743.936 Da average and 743.4568 Da monoisotopic below parent; it is the direct product of a failed or omitted conjugation and it is invisible to a backbone-only identity check, because the backbone is precisely what such a check confirms. Over-acylated species carrying a second side chain on Lys16, C262H413N51O80, 5557.463 / 5553.98168, the same interval above parent. Positional isomer acylated at Lys16 rather than Lys20: identical formula, identical exact mass at every decimal place, undetectable by any mass spectrometer at any resolving power, and found only by a peptide map or by a chromatographic method demonstrated to resolve the two isomers against a spiked standard. Des-amido, C-terminal free acid instead of the specified amide, C225H347N47O69, 4814.511 / 4811.50887, exactly plus 0.984 Da and invisible below about 30,000 resolving power. Aib substitution: alanine for Aib at position 2 or 13 is minus 14.0157 Da monoisotopic per position and minus 28.03 for both; Aib is non-proteinogenic, costs more and couples worse than alanine, so substituting it is the cheapest way to make something that resembles the molecule. Linker error: a one-AEEA linker gives a side chain 145.16 Da lighter and is retatrutide's architecture, not this one's. Salt form: the acetate is the commercial default, mono-acetate 4873.579, and adds 60.05 Da per counterion to the labeled mass basis.
2 Class & testing panel
- Form
- Single article
- Testing panel
- P2 — panel definitionwith mandatory P3 additions
3 Primary sources & evidence
A large sponsor-controlled clinical program exists and is recorded by study type, size and identifier only, with no reported outcome restated. Preclinical receptor pharmacology with first-in-human proof of concept: Coskun T et al., Mol Metab 2018, PMID 30473097. Human mechanistic study: Urva S et al., Diabetes Obes Metab 2020, PMID 32519795. Human randomized phase 3 trials: SURMOUNT-1, Jastreboff AM et al., NEJM 2022, PMID 35658024, 72 weeks; SURMOUNT-5, Aronne LJ et al., NEJM 2025, PMID 40353578, active comparator; SURMOUNT-OSA, Malhotra A et al., NEJM 2024, PMID 38912654; SUMMIT, Packer M et al., NEJM 2025, PMID 39555826, n=731. The SURPASS phase 3 program supported the 2022 approval; individual SURPASS PMIDs were not independently verified and none is printed here, because an unverified identifier is worse than none. The molecule also serves as active comparator in registered phase 3 trials of other compounds, including NCT06662383, NCT06221969, NCT06534411 and NCT06131437. The approved labeling carries a boxed warning and a warnings-and-precautions list; their content is not reproduced here, and the label at revision 02/2026 is the authoritative text. The entire human evidence base concerns investigational or approved material made under an approved application, not any article sold in the research-chemical market, and no independent published identity confirmation, impurity profile or stereochemical analysis of gray-market "tirzepatide" was located.
4 Storage & specification
- Storage
- Lyophilized powder at minus 20 degrees C plus or minus 5 degrees C, desiccated and protected from light, with the C20 fatty diacid side chain making the article surface-active and prone to adsorptive loss in dilute solution, so glass and low-binding plasticware rather than ordinary polypropylene.
- Shelf life
- The interval is dated on the acyl side chain rather than on gross purity, because the two attributes that move first on an acylated incretin analog are des-acylation at the 743.936 Da interval and hydrolytic loss of the C-terminal amide at 0.984 Da, and neither is visible in an area-percent figure. Each lot is placed on a stability protocol that tracks those two mass intervals, and the interval a lot carries is the one that protocol supports rather than one read off an area-percent purity figure.
This record reports identity, specification and study design. It does not state what the article does in a human body. Supplied under the caution: “CAUTION: Contains a new drug for investigational use only in laboratory research animals or for tests in vitro. Not for use in humans.”
