What Is Retatrutide? Chemical Structure, Receptor Profile, and Laboratory Handling Reference

WARNING: LABORATORY RESEARCH USE ONLY. This material is synthesized and distributed strictly for B2B development, laboratory research, and analytical studies. It is not a drug, dietary supplement, or cosmetic. Under no circumstances is this chemical compound intended for human or veterinary diagnostic or therapeutic application. All research must be conducted by qualified laboratory personnel using appropriate safety controls.

Last reviewed: 2026-08-15 · Research use only.

Retatrutide (research designation LY3437943) is a synthetic 39–amino-acid peptide studied in molecular pharmacology as a single-molecule agonist of three distinct human hormone receptors. This page is the canonical chemical reference for Retatrutide: its verified specifications, in vitro receptor profile, and laboratory handling protocols for research personnel. For a side-by-side chemistry comparison against related peptides, see how Retatrutide, Tirzepatide, and Semaglutide compare on receptor selectivity and molecular parameters.

1. Retatrutide Chemical Profile & Specifications

Retatrutide is a 39–amino-acid synthetic peptide bearing a C20 fatty-diacid moiety conjugated through a γ-glutamate / AEEA linker. When procuring reference material for laboratory assays, analytical purity is essential to reproducibility.

Note on purity, content, and excipients: these are three different things and are widely conflated. HPLC purity describes the peptide fraction — what proportion of the peptide-related material detected is the target sequence. Content (mass) assay describes how many milligrams of peptide are actually in the vial. Vialed lyophilized peptide is frequently formulated with excipients/fillers, so material can be high-purity by peptide assay while peptide is a minority of total vial mass. On our lot 06242026, for instance, HPLC peptide purity was 99.8% while the vial held 22.2 mg of peptide against 64.6 mg of excipients (1:2.9) in 86.8 mg total. Read purity and content as separate figures, and check whether excipients are reported — see the full Certificate of Analysis for lot 06242026 for a worked example.

Note on sterility: a Certificate of Analysis of the FTIR/HPLC type establishes identity, purity, and composition. It does not establish sterility, and typically states as much explicitly — analyses of this kind provide no information on particulate matter, microbial contamination, or endotoxins. Do not infer sterility, endotoxin limits, or microbial status from a chemical CoA; those require separate assays that must be requested and documented independently.

Why reported molecular weights for Retatrutide differ

Sources quote at least six different masses for this molecule. Almost all of them are correct — they are simply masses of different things. The table below maps each circulating figure to what it is actually the mass of. The molecular formula itself, C₂₂₁H₃₄₂N₄₆O₆₈, is not in dispute: PubChem, ChEMBL, the FDA Global Substance Registration System (GSRS) and the published InChI string all agree on it.

On the "39-amino-acid" mass. GSRS registers Retatrutide as a protein, so its primary record carries the bare peptide sequence and a backbone formula — the fatty-diacid linker, the two Aib residues and the α-methyl-leucine are not represented in it. Two backbone figures can be computed from that record: ≈ 4091.5 Da, from the free-acid formula GSRS states (C₁₈₇H₂₈₁N₄₃O₆₀), and ≈ 4090.6 Da, if the C-terminus is instead treated as the amide that GSRS's own systematic name calls for (it ends -L-serinamide). Queried live on 2026-08-12, GSRS's own calculated-weight field — checked on both the Retatrutide and Retatrutide-sodium UNII records, NOP2Y096GV and LQ42M82ZU6 — reports 4091.546 Da: the free-acid value, not the amide-corrected one. GSRS's formula and its own calculator agree with each other; the inconsistency is narrower than a prior version of this note stated — it sits between GSRS's name (which implies an amide) and its formula/calculated weight (which use the free acid), not between two different calculated values. Neither figure is the molecular weight of Retatrutide. Both describe the peptide chain before the lipid side chain is attached, and a supplier quoting one as a product specification has quoted the wrong molecule.

A value to discard: C₂₂₈H₃₅₀N₄₈O₆₆ / ≈ 4894.58 Da. This pair circulates on peptide reference pages and has appeared in AI-generated answers, but it does not survive checking, and earlier versions of this page repeated it — that was our error, and this note replaces it. The formula returns zero matches against PubChem's entire compound corpus, so it describes no known substance. It is also internally inconsistent: C₂₂₈H₃₅₀N₄₈O₆₆ computes to ≈ 4819.58, not 4894.58 — a 75 Da mismatch between a formula and the weight printed beside it. And the 163.25 Da gap from 4731.33 corresponds to no counterion used in peptide manufacture (TFA 114.02, acetate 60.05, Na⁺ 21.98, HCl 36.46), so the usual "it must be a salt form" explanation — which this page previously offered — is arithmetically impossible. We could locate no primary literature and no authoritative database carrying it. Do not use it, and treat a supplier datasheet that prints it as evidence that the datasheet was not checked.

For any specific material received, the batch-specific Certificate of Analysis (CoA) governs: it states which form was assayed and by which method, and a lot certificate supersedes any general value — including this table.

2. Molecular Pharmacodynamics: Triple Receptor Agonist Profile

In receptor-signaling assays, Retatrutide is classified as a unimolecular GIP, GLP-1, and glucagon (GCG) receptor tri-agonist, activating three human receptors in cell-based models.

Figure: Retatrutide receptor-engagement map — a single molecule activating three separate human receptors (GIP, GLP-1, glucagon/GCGR), with in vitro cAMP EC50 values per Coskun et al. (2022). Text-only version:

                  ┌───► GIP receptor    (glucose-dependent insulinotropic polypeptide)
                  │
Retatrutide ──────┼───► GLP-1 receptor  (glucagon-like peptide-1)
                  │
                  └───► Glucagon receptor (GCGR)

In Vitro Receptor Potency (cAMP EC50)

Values reported by Coskun et al. (2022) in cyclic-AMP accumulation assays using cells expressing each human receptor:

• GIP receptor: EC50 ≈ 0.064 nM — the most potent of the three interactions.
• GLP-1 receptor: EC50 ≈ 0.775 nM.
• Glucagon receptor (GCGR): EC50 ≈ 5.79 nM.

This tri-agonist profile makes Retatrutide a subject of interest for laboratory study of multi-receptor signaling and downstream cAMP pathways in transfected cell lines. Its three-receptor selectivity is the key chemical distinction from dual-agonist (Tirzepatide) and mono-agonist (Semaglutide) peptides.

3. Laboratory Handling & Reconstitution Guidelines

To preserve the structural integrity of lyophilized Retatrutide during assay preparation, follow standard peptide-handling protocols.

Storage

• Long-term (lyophilized): store at -20°C or lower (e.g., -80°C); protect from moisture.
• Short-term (reconstituted): aliquot and store at 2–8°C for limited-duration use; freeze individual aliquots at -80°C and avoid repeated freeze-thaw cycles.

Reconstitution for in vitro assays

Prepare stock solutions using standard laboratory solvents — sterile water, deionized water, or phosphate-buffered saline (PBS).

1. Bring the vial to room temperature (≈ 20–22°C) before opening to prevent condensation.
2. Wipe the stopper with a sterile isopropyl-alcohol wipe.
3. Add solvent slowly, directing the stream down the inner glass wall of the vial rather than onto the powder cake.
4. Swirl gently until fully dissolved into a clear, colorless solution. Do not shake — agitation can cause peptide aggregation and denaturation.

4. HPLC Purity & Quality Verification

Analytical documentation establishes two distinct properties of a research peptide — purity and identity — usually by different methods:

• Purity — HPLC. Chromatographic separation quantifies the target sequence against synthesis byproducts and truncated-peptide impurities, reported as a percentage of the peptide fraction. The acceptance criterion is printed on the certificate; read the assayed result against it rather than against a vendor's general claim. The figure is an area percent, and it is only interpretable alongside the method that produced it — see what "99% purity by HPLC" means and what must be stated beside it.
• Content (mass) — HPLC. A quantitative assay of how many milligrams of peptide the vial contains, checked against the label claim. Distinct from purity (see the note in §1).
• Identity — MS or FTIR. Mass spectrometry confirms the measured mass matches the theoretical mass for the intended sequence and fatty-acid linker. Fourier-transform infrared spectroscopy (USP ⟨197A⟩) instead confirms the compound via characteristic absorption bands. Certificates vary in which they use, and the two are not interchangeable evidence — check which method your lot's certificate actually reports rather than assuming MS.
• Composition — peptide-to-excipients ratio. Where the material is formulated, the certificate may report the peptide:excipient mass ratio (USP ⟨1151⟩).

A batch-specific Certificate of Analysis documents these results per lot, and a lot certificate supersedes any general product description for the material it covers. Boss BioTech USA publishes its certificates in full rather than gating them: see the complete Certificate of Analysis data for Retatrutide lot 06242026, transcribed alongside the downloadable certificate. A B2B sourcing & verification guide — covering how to evaluate a supplier and request lot-specific documentation — is in development and will be linked here at launch.

5. Frequently Asked Questions

Q: What is Retatrutide? A: Retatrutide (LY3437943) is a synthetic 39–amino-acid peptide that acts in vitro as a triple agonist of the human GIP, GLP-1, and glucagon receptors. It is a laboratory research reagent only.

Q: What is the CAS number of Retatrutide? A: The CAS registry number for Retatrutide (LY3437943) is 2381089-83-2.

Q: What receptors does Retatrutide target in vitro? A: It is a triple agonist of the human GIP, GLP-1, and glucagon (GCG) receptors, studied for laboratory research only.

Q: How should lyophilized Retatrutide be stored? A: Store lyophilized material at -20°C or lower for long-term stability; keep reconstituted aliquots at 2–8°C short-term and freeze aliquots at -80°C to avoid freeze-thaw degradation.

Q: Why do sources list different molecular weights for Retatrutide? A: Because they are quoting masses of different things. Four mechanisms account for essentially every figure in circulation. (1) What is included: the whole lipidated molecule is ≈ 4731.4 g/mol, while the 39-amino-acid backbone alone — the fatty-diacid/γ-Glu/AEEA side chain omitted, as on the FDA GSRS protein record — is ≈ 4090–4092 Da, about 640 Da lighter. (2) Which mass convention: average mass ≈ 4731.4, PubChem's exact mass 4730.4785 Da, and monoisotopic mass 4728.4718 Da are three different quantities for the same molecule. (3) Salt form: each trifluoroacetate counterion adds ≈ 114.02, each acetate ≈ 60.05, each sodium ≈ 21.98. (4) Charge state: an ESI-MS readout near 1183 is [M+4H]⁴⁺, not a molecular weight. A smaller 4731.33–4731.42 spread simply reflects which atomic-weight table was used. The formula C₂₂₁H₃₄₂N₄₆O₆₈ itself is not disputed. Confirm the form assayed against the CoA for the specific batch.

Q: What is the monoisotopic mass of Retatrutide, and how does it differ from the exact mass? A: PubChem lists a monoisotopic mass of 4728.4718 Da and an exact mass of 4730.4785 Da for C₂₂₁H₃₄₂N₄₆O₆₈. They differ by ≈ 2.007 Da, which is exactly 2 × (¹³C − ¹²C): the monoisotopic value is the all-¹²C species, while PubChem defines exact mass as the most intense peak of the isotope envelope, and for a 221-carbon molecule that peak carries two ¹³C atoms. High-resolution MS work normally means the monoisotopic figure, so quoting PubChem's exact mass in its place introduces a 2 Da error.

Q: Is the mass of the 39-amino-acid sequence the same as Retatrutide's molecular weight? A: No. Retatrutide is a lipidated peptide, and the 39-residue chain accounts for only part of its mass. The FDA GSRS record registers it as a protein and states a backbone formula (C₁₈₇H₂₈₁N₄₃O₆₀, ≈ 4091.5 Da) that omits the C20 fatty-diacid, the γ-Glu/AEEA linker, the two Aib residues and the α-methyl-leucine. The intact molecule is ≈ 4731.4 g/mol — roughly 640 Da heavier. A backbone figure quoted as a product specification describes the wrong molecule.

Q: What purity standard applies to research-grade Retatrutide? A: Purity is lot-specific and is documented on a batch Certificate of Analysis, which prints both the acceptance criterion and the assayed result. Boss BioTech USA's lot 06242026 assayed at 99.8% by HPLC peptide assay against a ≥98% specification. Note that HPLC purity describes the peptide fraction, not the peptide's share of total vial mass.

Q: Does a Retatrutide Certificate of Analysis prove the material is sterile? A: No. An FTIR/HPLC certificate establishes identity, purity, and composition only; such analyses state that they provide no information on particulate matter, microbial contamination, or endotoxins. Sterility and endotoxin status require separate assays documented independently.

Q: How much actual peptide is in a vial of lyophilized Retatrutide? A: Less than the total vial mass whenever the material is formulated with excipients. The content assay on the batch CoA gives the peptide mass; the peptide-to-excipients ratio gives the composition. On lot 06242026 that was 22.2 mg of peptide against 64.6 mg of excipients (1:2.9) in 86.8 mg total.

6. Scholarly References

1. Coskun, T., et al. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metabolism, 34(9), 1234–1247.e9. https://doi.org/10.1016/j.cmet.2022.07.013
2. National Center for Biotechnology Information. PubChem Compound Summary, CID 171934787 (C₂₂₁H₃₄₂N₄₆O₆₈; molecular weight, exact mass, monoisotopic mass). https://pubchem.ncbi.nlm.nih.gov/compound/171934787
3. U.S. Food and Drug Administration / NCATS. Global Substance Registration System (GSRS) substance record for Retatrutide, UNII NOP2Y096GV. https://gsrs.ncats.nih.gov/ (cited for the registered 39-amino-acid sequence and backbone formula.)
4. European Molecular Biology Laboratory–EBI. ChEMBL compound record CHEMBL5590721 (molecular formula and average molecular weight). https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL5590721/
5. Jastreboff, A. M., et al. (2023). Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine, 389(6), 514–526. https://doi.org/10.1056/NEJMoa2301972 (cited strictly for historical context of the molecule's chemical development.)

Related references: What does "99% purity by HPLC" mean on a Certificate of Analysis? · Certificate of Analysis data for Retatrutide lot 06242026 (HPLC purity, content assay, FTIR identity) · Retatrutide vs Tirzepatide vs Semaglutide: receptor-selectivity and chemical comparison · a B2B sourcing & verification guide is in development and will be linked here at launch.

Disclaimer: Boss BioTech USA distributes chemical compounds solely for laboratory research and analytical development. All products, including Retatrutide, are not approved for human clinical use, diagnosis, prevention, treatment, or cure of any medical condition or disease. The purchaser assumes all risks associated with the handling, testing, and use of these materials.