Tirzepatide

At a glance

Strengths

10 mg, 20 mg and 30 mg

Also known as

LY3298176

CAS number

2023788-19-2

Molecular formula

C225H348N48O68

Molecular weight

4813 g/mol (FDA label: 4813.53 Da)

Sequence

Y-Aib-EGTFTSDYSI-Aib-LDKIAQ-K(gamma-Glu-2xAEEA-C20 diacid)-AFVQWLIAGGPSSGAPPPS-NH2 (39 residues; Lys20 acylated)

PubChem CID

166567236

What tirzepatide is

Tirzepatide is a dual agonist of the GIP receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R). Eli Lilly developed it under the code LY3298176 ¹. A 2020 study by Lilly scientists and academic collaborators examined how it engages each receptor ¹. The authors reported greater engagement of GIPR than GLP-1R, which they called imbalanced agonism. At GLP-1R they reported a preference for cAMP generation over beta-arrestin recruitment, which they called biased agonism ¹. A 2022 cryo-electron microscopy and molecular dynamics study examined the structural basis of this pharmacology. Its authors concluded that the fatty acid modification, together with the amino acid sequence, determines how the molecule acts at the two receptors ². These are cell-based and structural findings. Tirzepatide is related to retatrutide, which adds glucagon receptor activity, but the two have different sequences and masses.

Structure and chemical identity

According to its FDA label, tirzepatide is based on the GIP sequence. It contains 2-aminoisobutyric acid (Aib) at positions 2 and 13 and a C-terminal amide. The lysine at position 20 is attached to 1,20-eicosanedioic acid through a linker, which FDA's substance registry describes as a gamma-glutamic acid followed by two amino-ethoxy-ethoxy-acetic acid units. In PubChem, tirzepatide is CID 166567236: formula C225H348N48O68, molecular weight 4813 g/mol. The FDA label gives 4813.53 Da. The CAS number is 2023788-19-2. The C-terminal run of prolines matters for manufacture. During linear solid-phase synthesis, intermediates ending in Pro-Pro-Ser can form diketopiperazines, which leave double-amino-acid deletion impurities ³.

Regulatory status

FDA approved tirzepatide as Mounjaro on May 13, 2022 (NDA 215866) and as Zepbound on November 8, 2023 (NDA 217806). Both are Eli Lilly prescription medicines. The approved indications are set out in each medicine's FDA label, available through Drugs@FDA for Mounjaro and Zepbound. The tirzepatide sold here is not Mounjaro or Zepbound. No FDA approval covers its manufacture or quality, and it is sold only for laboratory research, never for use in people or animals.

Published research

The literature runs from receptor pharmacology to large trials, and the studies most useful for a laboratory are listed here by design.

• Receptor pharmacology (2020). Receptor occupancy modelling, signalling and internalisation assays, and primary islet experiments ¹.
• Structural biology (2022). Cryo-electron microscopy and molecular dynamics simulations of tirzepatide bound to its receptors ².
• Process chemistry (2022). A mechanistic study of diketopiperazine formation during solid-phase synthesis, with control strategies ³.
• Population pharmacokinetics (2024). A model built from 19 pooled studies ⁴.
• Analytical method (2026). A stability-indicating HPLC method tested under acidic and basic hydrolysis, oxidative and photolytic stress ⁵.

Lilly's phase 3 programmes for the approved medicines are named SURPASS and SURMOUNT. Their designs are registered on ClinicalTrials.gov, and this page does not summarise their results.

What is not known

Published clinical results cannot vouch for a powder synthesised elsewhere, whose identity, purity and stability have to be shown lot by lot. Synthesis route, counter-ion, peptide content and impurity profile can all differ between sources. The closest published work on degradation is the forced-degradation HPLC method above ⁵. A PubMed search found no study of how lyophilised research-grade tirzepatide changes during ordinary storage, so its solid-state degradation products and their rates of formation are undescribed.

Laboratory storage and handling

Store research tirzepatide as stated on the lot's certificate of analysis and product label. Zepbound's FDA label tells users to "Protect ZEPBOUND from heat and light", but that instruction belongs to the approved medicine, not to research powder. To avoid condensation on the powder, bring a cold vial to room temperature before the seal is broken. The lot number and opening date belong in the lab record.

Quality testing

A certificate of analysis for tirzepatide should confirm identity by mass spectrometry, with a measured mass consistent with about 4813 Da. That result also distinguishes tirzepatide from retatrutide, which has a molecular weight of about 4731 g/mol. Reversed-phase HPLC is the standard purity method, and a stability-indicating method separates tirzepatide from its stress degradants ⁵. The certificate is more useful when it includes the chromatogram rather than a single percentage. Peptide content, counter-ion and water content explain the gap between the weight of powder and the amount of peptide. One impurity class is documented for this molecule: double-amino-acid deletions that arise from diketopiperazine formation during solid-phase synthesis ³. Material in which the fatty diacid side chain is missing or incomplete is a general concern for acylated peptides. The certificate should say whether the method looked for both.