Skip to content
Peptides Codex
ENFR

Use the arrow keys to choose a result, Enter to open it, and Escape to close.

← Home
Endogenous opioid tetrapeptide

Endomorphin-2

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) is an endogenous opioid tetrapeptide and a highly selective mu-opioid receptor agonist. It differs from endomorphin-1 by one residue and is more prevalent in the spinal cord.

By The Peptides Codex Editorial TeamIndividual review date not recorded

Page data last changed: . Chemistry registry snapshot: . Registry refreshes and identity assessments are separate from scientific content review.

Length
4 aa
Class
Endogenous opioid tetrapeptide
Function
High-affinity, highly selective agonist of the mu-opioid receptor
Context
Endogenous neuropeptide and research tool in opioid pharmacology; not a Health Canada-authorized product

The spinal-cord counterpart to endomorphin-1, differing by a single aromatic residue.

Also known as: EM-2

Part of the Neuropeptides & signaling cluster

Overview

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) is an endogenous opioid tetrapeptide and a highly selective mu-opioid receptor agonist. It differs from endomorphin-1 by one residue and is more prevalent in the spinal cord. It is used as a research tool, and this page is educational only.

Source & context

Biological / chemical source: Mammalian central nervous system (endogenous), enriched in spinal cord

Primary research or clinical context: Endogenous neuropeptide and research tool in opioid pharmacology; not a Health Canada-authorized product

One-residue difference

Endomorphin-2 shares the Tyr-Pro-Phe-Phe-NH2 scaffold with endomorphin-1 but replaces the third-position tryptophan with phenylalanine. Both are amidated tetrapeptides with high mu-opioid selectivity, but endomorphin-2 is comparatively enriched in the spinal cord, making the pair a useful lesson in how small sequence changes shape distribution and pharmacology.

Research role and limits

Endomorphin-2 is used in laboratory studies of opioid receptor signalling and spinal analgesia in animal models. Like endomorphin-1 it is rapidly degraded and poorly brain-penetrant, so it remains a research probe rather than a medicine. This page is educational and makes no claim about pain or any medical use.

Structure & chemistry

Molecular identity & reference confidence

Source-supported reference

The four-residue chains agree. -NH2 records the C-terminal amide described in the IUPHAR snapshot and PubChem structure. Bare sequence arithmetic omits that modification.

Molecular form
Endomorphin-2, amidated tetrapeptide
Species
Not established by this molecular identity audit
Termini (N / C)
Not specified / Amide

Average reference mass · Molecular identity assessment: 2026-10-05

Reference policy updated: 2026-10-05

Molecular formula
C32H37N5O5
Average reference mass
≈ 571.7
C-terminus
Amide
Identifiers

Chemistry values: PubChem, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.

Concentration math

Endomorphin-2 — reconstitution calculator

Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.

Reference form: Endomorphin-2, amidated tetrapeptideAverage reference mass: 571.7 Da

Syringe graduation
Solution concentration
5 mg/mL5,000 mcg/mL
mcg

Enter an amount to see the volume it corresponds to.

Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.

Open the Endomorphin-2 calculator on its own page →

FAQ about Endomorphin-2

What is Endomorphin-2?+

Endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) is an endogenous opioid tetrapeptide and a highly selective mu-opioid receptor agonist. It differs from endomorphin-1 by one residue and is more prevalent in the spinal cord. It is used as a research tool, and this page is educational only.

What Canadian product status is recorded for Endomorphin-2?+

Canadian product status for Endomorphin-2 has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.

What is the typical length of Endomorphin-2?+

Endomorphin-2 is commonly described as approximately 4 amino acids (Endogenous opioid tetrapeptide).

Related peptides

Motilin
Gut hormone
Motilin is a 22-amino-acid gut hormone secreted by endocrine cells of the small intestine. It coordinates the migrating motor complex, the wave of contractions that clears the digestive tract between meals, earning it the nickname the housekeeper of the gut.
Obestatin
Gut hormone
Obestatin is a 23-amino-acid peptide cleaved from the same preproghrelin precursor that produces ghrelin. It was originally proposed to oppose ghrelin's appetite-stimulating effects, though its physiology and receptor remain actively debated in the research literature.
Albiglutide
Incretin mimetic (GLP-1 receptor agonist)
Albiglutide is a GLP-1 receptor agonist created by genetically fusing two modified GLP-1 sequences to human serum albumin, giving it a long half-life suited to once-weekly dosing. Approved as Tanzeum and Eperzan in 2014, it was later withdrawn from the market for commercial reasons and is now a historical case study.
Neurotensin
Neuropeptide
Neurotensin is a 13-amino-acid neuropeptide found in the brain and gut. Research examines its interactions with dopamine signaling and its roles as a neuromodulator and local hormone.

References & further reading

  1. 1.Wang et al. (2024). Endomorphin-2 analogs with C-terminal esterification display potent antinociceptive effects in the formalin pain test in mice. Peptides
  2. 2.Tseng (2002). The antinociceptive properties of endomorphin-1 and endomorphin-2 in the mouse. Jpn J Pharmacol
  3. 3.Huo et al. (2023). A novel endomorphin-2/salmon calcitonin hybrid peptide with enhancing anti-allodynic and anti-anxiety effects. Peptides
  4. 4.Narita et al. (2002). Endomorphin-induced motivational effect: differential mechanism of endomorphin-1 and endomorphin-2. Jpn J Pharmacol
  5. 5.Liu et al. (2019). Effect of endomorphin-2 on orofacial pain induced by orthodontic tooth movement in rats. Eur J Oral Sci
  6. 6.Kruszynski et al. (2005). Novel endomorphin-2 analogs with mu-opioid receptor antagonist activity. J Pept Res
  7. 7.Fujita et al. (2006). Inhibition by endomorphin-1 and endomorphin-2 of excitatory transmission in adult rat substantia gelatinosa neurons. Neuroscience
  8. 8.Kamei et al. (2000). The antinociceptive effects of endomorphin-1 and endomorphin-2 in diabetic mice. Eur J Pharmacol
  9. 9.PubMed — Endomorphins and related opioid peptides (review, 12481550)
  10. 10.Wikipedia — Endomorphin-2
Disclaimer: Educational content only. Not medical advice. Not instructions for human use. Research peptides and unapproved products may be restricted or illegal to market for human consumption in your jurisdiction. Consult qualified professionals and applicable law.
You might also like: All peptides · Atlas · Research · Tools
Cite this: Peptides Codex — Endomorphin-2 educational profile.
Tip: Use browser print (Ctrl/Cmd + P) for a clean PDF of this page.