EM66
A 66-amino-acid peptide cut from the same granin protein as secretoneurin — a brain appetite signal and a sensitive blood marker for adrenal tumours. A research peptide, not a drug
EM66 is a 66-amino-acid peptide released from secretogranin II, one of the granins — the acidic proteins packed inside the secretory granules of nerve and endocrine cells. The same precursor yields the better-known peptide secretoneurin, and EM66 sits right beside it; its sequence has been conserved almost unchanged across animals from fish to humans, a strong hint that it does something important. Research gives EM66 two faces. In the brain it is an appetite-regulating (anorexigenic) neuropeptide: its neurons populate the feeding-control nuclei of the hypothalamus, fasting changes how much of it is made, and it appears to act through the same POMC and NPY systems that govern hunger and fullness. In the body it is a clinical marker: EM66 is stored in the chromaffin cells of the adrenal gland, its release is driven by the signalling peptide PACAP, and in people with pheochromocytoma — tumours of those cells — blood EM66 rises about ten-fold and tissue levels help tell benign from malignant tumours. EM66 is studied as a research peptide and a diagnostic marker; it is not an approved medicine and has not been given to people as a treatment.
No established human dose Details ↓
Recommended Dosing
No established human dose
EM66 is an endogenous secretogranin-II-derived peptide that has never been given to people as a treatment. The human studies measure the body's own EM66 as a marker, and the functional work is in animals and cells.
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What is it?
The granins are a family of acidic proteins stored in the secretory granules of nerve and endocrine cells, where they are cut into many smaller active peptides. Secretogranin II (SgII) is one of them, and its best-known product is secretoneurin. Beside secretoneurin, within the same precursor, lies EM66 — a 66-amino-acid peptide whose sequence has stayed remarkably constant across the vertebrates, from fish to humans, which usually signals a conserved and important function.
In the brain, EM66 behaves as an appetite-regulating peptide. Its neurons are concentrated in the feeding-control nuclei of the hypothalamus — the arcuate, paraventricular and preoptic areas and the lateral hypothalamus. When animals are deprived of food, the amount of EM66 (and its precursor SgII) in these regions changes: fasting increases the number of EM66-containing neurons in the arcuate and paraventricular nuclei of the jerboa, and in rats four days of food deprivation alters SgII expression alongside the hunger peptide NPY and the satiety peptide POMC. This positions EM66 as a novel anorexigenic (appetite-reducing) neuropeptide that works in concert with the established POMC and NPY systems.
In the body, EM66 is a clinically useful marker. It is stored in the chromaffin cells of the adrenal medulla — the cells that make adrenaline — and in people with pheochromocytoma, the tumours of those cells, circulating EM66 is roughly ten-fold higher than in healthy volunteers and falls back to normal after the tumour is removed. Tissue EM66 is markedly higher in benign than in malignant tumours, so measuring it helps doctors tell the two apart and follow patients over time — a sensitivity that compares well with the standard metanephrine tests.
How EM66 gets out of cells has been worked out in chromaffin-cell cultures: the pituitary peptide PACAP drives its release through several signalling routes at once — calcium entry through L-type channels, and the PKA, PKC and MAP-kinase cascades — suggesting EM66 acts downstream of the nerve signals that switch on the adrenal gland. Its lower levels in malignant pheochromocytoma track with reduced SgII gene transcription and less of the processing enzymes that liberate the peptide.
EM66 is an endogenous secretogranin-II-derived research peptide and diagnostic marker. No published study has given EM66 to people as a treatment — the human work measures the body's own peptide, and the functional work is in animals and cells — it is approved nowhere, and material sold online as 'EM66' is an unregulated research chemical. Nothing here is a dose or a therapy; this page records what the published science says about the peptide.
Mechanism of Action
EM66 is a 66-amino-acid peptide cut from secretogranin II, beside secretoneurin. In the hypothalamus it acts as an anorexigenic neuropeptide through the POMC/NPY systems; in the adrenal and pituitary it is stored in secretory granules and released from chromaffin cells under PACAP control, and it serves as a sensitive circulating marker for pheochromocytoma.
Secretogranin-II processing
EM66 is generated by proteolytic processing of secretogranin II, the same precursor that yields secretoneurin, and is stored with it in secretory granules of endocrine and chromaffin cells (PMID 12871990).
Anorexigenic feeding control
EM66 neurons occupy the hypothalamic feeding nuclei; food deprivation changes EM66/SgII expression alongside NPY and POMC (PMIDs 28902709, 15929742), marking it as an appetite-reducing neuropeptide.
Chromaffin secretion and tumour marking
PACAP drives EM66 release from chromaffin cells via calcium, PKA, PKC and MAP-kinase (PMID 16963134); in pheochromocytoma, circulating and tissue EM66 track tumour status (PMIDs 16287097, 12788858).
Published Research
These are studies of EM66 read from their PubMed abstracts on November 6, 2026. They include human studies of circulating and tissue EM66 as a pheochromocytoma marker, animal studies of its hypothalamic expression and its modulation by food deprivation, a biochemical characterisation and localisation study, and a cell study of how PACAP drives its secretion. The human work measures the body's own EM66; EM66 has not been given to people as a treatment.
Circulating EM66 is a sensitive marker for pheochromocytoma
In patients with pheochromocytoma, plasma EM66 was about ten-fold higher than in healthy volunteers and returned to normal after the tumour was removed, while urinary EM66 was unchanged. The plasma EM66 test was more sensitive than plasma or urinary metanephrine measurements taken separately, and tumour cells in culture secreted high levels — supporting circulating EM66 as a complementary marker for diagnosing and following pheochromocytoma (a human observational study).
Tissue EM66 discriminates benign from malignant pheochromocytoma
EM66 was detected by immunohistochemistry and radioimmunoassay in benign and malignant pheochromocytoma tissue, restricted to chromaffin cells. Concentrations were far higher in benign (median 25.6 ng/mg protein) than malignant (median 3.8 ng/mg protein) tumours, suggesting that measuring EM66 may help identify patients at higher risk of tumour progression (a human observational study).
Food deprivation changes hypothalamic EM66 expression in rat
In rats, four days of food deprivation significantly increased hypothalamic secretogranin II (the EM66 precursor) and NPY messenger RNA and decreased POMC messenger RNA, while two or three days had no effect. The authors conclude that EM66 gene expression is driven by negative energy balance and interacts with the NPY and POMC systems to regulate food intake (a preclinical result).
Hypothalamic EM66 is modulated by fasting in the jerboa
In the jerboa, EM66-producing neurons were widely distributed across the hypothalamus, and five days of food deprivation significantly increased the number of EM66-containing neurons in the arcuate nucleus (+105%) and the parvocellular paraventricular nucleus (+115%) — evidence that the EM66 system shows physiological plasticity and is implicated in the control of feeding behaviour and the response to fasting (a preclinical result).
Characterisation and localisation of EM66 in rat glands
Biochemical and immunocytochemical study showing that processing of secretogranin II generates EM66, which in the rat pituitary is stored in the secretory granules of gonadotrophs, lactotrophs, thyrotrophs and melanotrophs (not corticotrophs) and in the adrenal medulla occurs specifically in adrenaline-making chromaffin cells — a cell-specific distribution supporting a role for EM66 in the endocrine system (a mechanistic study).
PACAP drives EM66 secretion from chromaffin cells
In cultured bovine adrenal chromaffin cells, the peptide PACAP dose-dependently stimulated EM66 release through multiple signalling pathways acting together — calcium entry through L-type channels, and the PKA, PKC and MAP-kinase cascades — with blockade of all of them abolishing the response. This indicates EM66 is co-stored with secretoneurin in chromaffin granules and released downstream of neurocrine stimulation of the adrenal medulla (a cell study).
No Established Human Dose
EM66 is an endogenous secretogranin-II-derived peptide that has never been given to people as a treatment. The human studies measure the body's own EM66 as a marker, and the functional work is in animals and cells. No regulator has approved any dose, and no published human dose exists, so no amount is printed here.
What this rests on: PMID 16287097, PMID 12788858, PMID 28902709.
Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes EM66 is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
Unknown: no human dose of EM66 has been established (see No Established Human Dose below), so there is no amount to work out. The reconstitution calculator does the arithmetic for any vial, water and dose.
Storage before and after mixing
Unknown: no label or published stability study on file says how to store EM66, before or after mixing. The mixing guide sets out the general rules, with their sources: keep a mixed vial in the fridge, and use it promptly, as the bacteriostatic water label says of any drug dissolved in it. The 28 days often quoted is the limit for an opened multiple-dose vial from a manufacturer, an outer limit set for sterility, not a time a mixed solution has been shown to keep. Nobody has published how long EM66 stays intact once mixed.
How it is taken
Unknown: with no established human dose, there is no established way of taking EM66. What the human studies gave and how is set out under No Established Human Dose.
What to expect, and when
How long it stays in the body: a half-life of not established for humans as a drug; an endogenous granin peptide. After about five half-lives almost none is left.
When effects appear: unknown; no source on this page gives a time to effect for EM66. Results reported in the studies are under Published Research.
Source: half-life: PMID 16963134.
Side effects, and when to stop or get help
From the Side Effects section: No human adverse-event data exist: no published study has administered EM66 to people; The human studies measure endogenous EM66 as a pheochromocytoma marker, not as a treatment (PMIDs 16287097, 12788858); In animals it is an appetite-regulating hypothalamic peptide (PMIDs 28902709, 15929742) — a physiological role, not a human safety profile; Material sold online as 'EM66' is an unregulated research chemical of unverified content. Full list and cautions ↓
When to stop or get help: unknown; no label or trial on file sets rules for stopping EM66. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“EM66 is a research peptide and diagnostic marker that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status”).
Interactions
Unknown: a PubMed search for human interaction studies of EM66 (reviewed 2026-11-06) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of EM66 products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: Research Chemical (Not a drug: Drugs@FDA and the openFDA label endpoint hold no record, and FDA GSRS and ChEMBL hold no substance record for EM66 (searched November 6, 2026)). Sport: Not on the 2026 List.
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
EM66 is a research peptide and diagnostic marker that has not been given to people as a drug, so there is no human safety profile; the points below reflect that research status.
Contraindications & Cautions
EM66 has no approved use and no label. These points reflect its research status.
Legal Status
EM66 is an endogenous secretogranin-II-derived peptide studied as a research compound and diagnostic marker; it is not a drug and is not approved in any country.
Frequently Asked Questions
?What is EM66?
A 66-amino-acid peptide cut from secretogranin II — the same granin protein that yields secretoneurin. Its sequence is highly conserved across animals.
?What does it do?
In the brain it is an appetite-reducing (anorexigenic) neuropeptide that works with the POMC and NPY systems (PMID 28902709), and in the body it is a sensitive blood and tissue marker for pheochromocytoma, the adrenal chromaffin tumour (PMIDs 16287097, 12788858).
?How is it related to secretoneurin?
Both EM66 and secretoneurin are cut from the same precursor, secretogranin II, and are co-stored and co-released from secretory granules. Grey Peptides has a separate entry for secretoneurin.
?Is it approved or available to buy?
No. EM66 is not a medicine, has no FDA application or label, and is approved nowhere; it is studied as a research peptide and a diagnostic marker. Material sold online as EM66 is an unregulated research chemical. Grey Peptides lists no sellers and recommends no source; this page records the published science.
References
- [clinical-trial] Guillemot J, et al. "Circulating EM66 is a highly sensitive marker for the diagnosis and follow-up of pheochromocytoma." Int J Cancer, 2006;118(8):2003-12. PMID: 16287097.
- [clinical-trial] Yon L, et al. "Identification of the secretogranin II-derived peptide EM66 in pheochromocytomas as a potential marker for discriminating benign versus malignant tumors." J Clin Endocrinol Metab, 2003;88(6):2579-85. PMID: 12788858.
- [animal] Trebak F, et al. "Effect of food deprivation on the hypothalamic gene expression of the secretogranin II-derived peptide EM66 in rat." Neuroreport, 2017;28(16):1049-1053. PMID: 28902709.
- [animal] Boutahricht M, et al. "Biochemical characterisation and immunohistochemical localisation of the secretogranin II-derived peptide EM66 in the hypothalamus of the jerboa (Jaculus orientalis): modulation by food deprivation." J Neuroendocrinol, 2005;17(6):372-8. PMID: 15929742.
- [mechanism] Montero-Hadjadje M, et al. "Biochemical characterization and immunocytochemical localization of EM66, a novel peptide derived from secretogranin II, in the rat pituitary and adrenal glands." J Histochem Cytochem, 2003;51(8):1083-95. PMID: 12871990.
- [mechanism] Guillemot J, et al. "Involvement of multiple signaling pathways in PACAP-induced EM66 secretion from chromaffin cells." Regul Pept, 2006;137(1-2):79-88. PMID: 16963134.
- [other] UniProt P13521 (secretogranin-2, SCG2 gene), read November 6, 2026: EM66 is a 66-amino-acid peptide generated by proteolytic processing of secretogranin II, the same granin precursor that yields secretoneurin; the EM66 sequence is highly conserved across vertebrates. https://www.uniprot.org/uniprotkb/P13521/entry
- [other] EM66 was named and characterised as a novel, highly conserved peptide flanking secretoneurin within secretogranin II; its 66-residue structure, its presence in the pituitary, adrenal and hypothalamus, and its roles as an anorexigenic neuropeptide and a pheochromocytoma marker are from the studies carded on this page (read November 6, 2026).
- [other] US FDA, Drugs@FDA and the drug label endpoint (openFDA), searched November 6, 2026: no application and no label record for EM66. It is an endogenous secretogranin-II-derived peptide, not a registered drug; FDA GSRS and ChEMBL hold no substance record for it.
Sources & Citations
The six studies carded above were read from their PubMed records on November 6, 2026. Identity comes from UniProt (P13521, secretogranin-2) and the studies carded here: EM66's origin as a 66-residue secretogranin-II fragment beside secretoneurin, its role as an anorexigenic hypothalamic neuropeptide acting with the POMC/NPY systems, its PACAP-driven secretion from chromaffin cells, and its use as a sensitive circulating and tissue marker for pheochromocytoma are from those studies; the absence of US approval and of a drug substance record from Drugs@FDA, openFDA, FDA GSRS and ChEMBL was checked the same day. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.