Last reviewed: October 2026 · Cleared Peptides research team
Research use only. Nisotirostide (LY3457263): Research Guide is supplied for laboratory research. It is not a drug, food, cosmetic, or dietary supplement. It is not FDA-approved. It is not for human or veterinary administration. This page does not give a dose or a method of administration. A study cited on this page describes that study’s own test article. It does not make this lot an approved medicine. To check a fact, open the PubMed or DOI link, confirm the authors and year, and match the paper’s compound name, CAS number, or sequence to the specification table. The full method is on the research desk page. Identity and purity for a lot are only what that lot’s certificate of analysis reports. An HPLC percentage is not a sterility result and not an endotoxin result unless the certificate prints those tests.
Nisotirostide (LY3457263) is a synthetic, lipidated analog of peptide YY (PYY). Native PYY(3–36) is a selective agonist of the neuropeptide Y2 receptor (Y2R), and nisotirostide is used in research on this receptor family alongside incretin-receptor peptides.
Nisotirostide Structure and Identifiers
| Name | Nisotirostide |
|---|---|
| Code | LY3457263 |
| CAS number | 2663844-45-7 |
| PubChem CID | 171921325 |
| Molecular formula | C230H343N59O65 |
| Molecular weight | ≈4974.6 g/mol |
| Class | Lipidated PYY analog peptide |
| Form | Lyophilized powder |
PYY and the Y2 Receptor
PYY is released from intestinal L-cells together with GLP-1. Cleavage of PYY(1–36) by DPP-4 yields PYY(3–36), which shows selectivity for Y2R, a Gi-coupled GPCR. Lipidation is used to extend peptide half-life.
Related Research Compounds
Compare with retatrutide, tirzepatide and semaglutide, which target incretin receptors rather than NPY receptors.
This summary describes laboratory research only and makes no claim about effects in humans or animals.
Purity Testing and Storage
Every lot of Nisotirostide supplied by Cleared Peptides is tested by an independent laboratory for identity and purity (or composition, for multi-component preparations), and the lot Certificate of Analysis is published on our COA page. Store lyophilized Nisotirostide at −20 °C, sealed, dry and protected from light. Allow the vial to reach room temperature before opening and minimize freeze–thaw cycles. Handle according to your institution’s chemical-hygiene procedures.
Research materials referenced in this guide
Analytical testing notes for Nisotirostide
Nisotirostide is identified in this guide as CAS 2663844-45-7, formula C230H343N59O65, listed mass ≈4974.6 g/mol. An identity test compares a measurement with those values. A mass spectrum is the usual measurement for a peptide. FTIR, when a certificate uses it, is a supporting infrared fingerprint and is less specific for closely related sequences.
Nisotirostide carries a fatty-acid or other lipophilic modification, so it is among the later-eluting peptides on a C18 column. Laboratories often raise the acetonitrile fraction, the column temperature, or move to a C8 or C4 column so the main peak is sharp enough to integrate. The mass used for identity has to include the lipid chain and linker, not only the amino-acid backbone. Area-percent purity still ignores water and counterion.
HPLC purity for this material is an area-percent result at the wavelength and gradient the laboratory states, commonly ultraviolet detection near 214 nm on a reversed-phase column. The instrument is a gradient pump, injector, column oven, and UV or diode-array detector. That percentage is not the number of milligrams in the vial. Water, acetate, trifluoroacetate, and other UV-silent material can dominate the gross weight while the purity figure stays high. Net peptide content, from an assay or amino-acid analysis, is the separate result to read when the certificate reports it.
A sterility test and an endotoxin test are not included in a chemical purity result. The compendial sterility test is a culture method (USP <71>): membrane filtration or direct inoculation into fluid thioglycollate medium and soybean-casein digest medium, incubated for 14 days. A PCR sterility screen uses a thermal cycler to detect microbial DNA and is a different method. The endotoxin test (USP <85> LAL, or USP <86> recombinant Factor C) reports endotoxin units with an incubating reader or a cartridge reader. Use a result only when that method is printed on the lot certificate. One published example in this catalog states that the report does not cover microbial contamination or endotoxins. The full description of equipment, standards, and how US laboratory accreditation works is in peptide analytical testing. Lot records are on the COA page.
Frequently Asked Questions
What receptor family does nisotirostide target?
Neuropeptide Y receptors, with PYY analogs typically selective for Y2R.
Is Nisotirostide for human use?
No. Cleared Peptides supplies Nisotirostide for laboratory research use only; it is not for human or veterinary use.
Written by the Cleared Peptides Research Desk, the editorial desk of Cleared Wellness Group LLC. This is not a personal profile of a physician or a scientist, and it is not a fictional author. The checking method is public on the research desk page. Last reviewed October 2026.
Nisotirostide research note: an NPY2 agonist, not a third incretin
Research use only. CP-Niso is lyophilized nisotirostide for laboratory research, development code LY3457263, CAS 2663844-45-7. It is not a GLP-1, GIP, or glucagon agonist, and it is not for human or veterinary administration. This note does not repeat the doses used in the phase 1 paper.
The paper that names it
Briere, Leohr, Linnebjerg, and colleagues (Molecular Metabolism, 2026) describe nisotirostide (LY3457263) as a selective agonist of the neuropeptide Y2 receptor, developed as an adjunct for people already taking a GLP-1 receptor agonist. The abstract reports in-vitro selectivity at human NPY2, mouse studies of body weight and glucose, and a phase 1 study in healthy participants and in participants with type 2 diabetes who were taking dulaglutide. Gastrointestinal events were the common adverse events in that study. Those are results inside that paper’s protocol. They are not results for this research lot. PubMed 42829171, DOI 10.1016/j.molmet.2026.102452.
This catalog’s specification calls the same code a lipidated analogue of peptide YY, formula C230H343N59O65, mass about 4974.6 g/mol. Peptide YY is an endogenous ligand at NPY2, so the catalog description and the paper’s receptor class point the same direction. They are still two texts. A reader should open Briere 2026 and confirm that the structure drawn there matches CAS 2663844-45-7 and the formula in the table before treating every sentence in the paper as a description of this vial. This note does not reproduce a residue-by-residue structure the certificate has not printed.
Why it is grouped near the GLP peptides, and why that grouping misleads
The phase 1 design studied nisotirostide on top of a GLP-1 drug. That is a clinical-development choice. It does not make the peptide an incretin. Retatrutide’s receptors are GIP, GLP-1, and glucagon. Nisotirostide’s receptor, in Briere’s title, is NPY2. An assay panel that only contains incretin receptors will not see the activity the paper claims, and an incretin certificate will not identify this mass.
How to verify this note
- Open the 2026 DOI and confirm the authors, the code LY3457263, and the words “NPY2 receptor agonist.”
- Match CAS 2663844-45-7 and mass about 4974.6 g/mol on the certificate. Retatrutide’s mass is about 4731. Those are not the same peak.
- Keep the phase 1 adverse-event and weight language inside the paper. It is not a label for this vial.
Selected References
Peer-reviewed literature on the compounds discussed in this guide, listed as scientific background for laboratory researchers. Citation does not imply endorsement by the authors or any use other than in-vitro research.
- Ghamari-Langroudi M, et al. PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors. Cell Metab. 2005;2(3):191-9. PubMed 16154101 · DOI
Laboratory note: solubility depends on salt form and solvent. This guide does not state a single solubility figure. Handling of lyophilized material is described in the peptide storage guide.
Research Use Only Notice
This guide is provided for educational and laboratory reference purposes. It summarizes published, primarily in-vitro and structural research literature and does not describe, recommend or imply any use in humans or animals. Products sold by Cleared Peptides are for laboratory research use only; they are not drugs, foods, cosmetics or dietary supplements, are not FDA-approved, and are not intended to diagnose, treat, cure, mitigate or prevent any disease. No dosing, administration or therapeutic information is provided.
