Hexarelin Research, Specifications & Scientific Information

Introduction

Hexarelin is a six-residue synthetic peptide, and almost everything interesting about it follows from two facts that sit oddly together. The first is that it is a growth hormone secretagogue — it releases growth hormone in humans through a receptor that has nothing to do with growth hormone-releasing hormone, and it does so more strongly than growth hormone-releasing hormone itself at comparable amounts ^[1]. The second is that its most-studied action in the heart does not involve that receptor at all, but a scavenger receptor called CD36 that was identified by photolabelling rat cardiac membranes with a radioactive derivative of the peptide ^[10].

Those are two separate pharmacologies in one molecule, and the literature on hexarelin divides along that seam. On one side sits a substantial body of human clinical pharmacology from the 1990s, most of it asking whether the compound could serve as a provocative test of pituitary function. On the other sits rodent cardiac work that has no human counterpart. This page keeps them apart, because evidence about one is not evidence about the other.

This page is a reference record. It describes research. It does not describe use in people or animals, and it contains no guidance of any kind on handling the material.

What Is Hexarelin?

Hexarelin is a synthetic hexapeptide amide of the growth hormone-releasing peptide series, written His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂ ^[2]. It carries the International Nonproprietary Name examorelin and the development code EP-23905, and it was developed at Mediolanum Farmaceutici in Milan, where several members of this peptide series originated.

Structurally it is a single methyl group away from GHRP-6. Both peptides run His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂; hexarelin adds a 2-methyl substituent to the D-tryptophan in position two. Two of the six residues are D-amino acids and the C-terminus is an amide, both of which slow enzymatic cleavage. The whole series was built by structure-activity work on met-enkephalin analogues that released growth hormone, long before anyone knew what receptor they acted at.

It is not an approved medicine in the United States and has not been approved by the U.S. Food and Drug Administration for any indication. Clinical pharmacology studies were published through the 1990s, several of them framed explicitly as an evaluation of the compound as a diagnostic stimulus rather than as a treatment, and no registrational programme has been identified in public trial registers.

Hexarelin Specifications

Hexarelin is a six-residue synthetic peptide amide built on the same backbone as GHRP-6, from which it differs by a single methyl group: the D-tryptophan at position 2 carries a 2-methyl substituent. That substitution has no single-letter representation, which is why the sequence above is written in three-letter code with the stereochemistry and the modification made explicit. Two of the six residues are D-amino acids and the C-terminus is an amide rather than a free acid; both features are deliberate and both reduce the rate at which the peptide is cleaved by aminopeptidases and carboxypeptidases. The molecular formula C47H58N12O6 and monoisotopic-derived average mass of 887.0 g/mol are the values carried by PubChem under compound identifier 6918297, which also records CAS registry number 140703-51-1 and the FDA/NCATS unique ingredient identifier 09QF37C617 under the International Nonproprietary Name examorelin. Material is commonly supplied as the acetate salt, whose mass differs from the figure above. Any identifier on this page is a reference value; the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Hexarelin Work?

The receptor is the growth hormone secretagogue receptor type 1a, a class A G protein-coupled receptor expressed on pituitary somatotrophs and in the hypothalamus. It was cloned from pituitary libraries as the target of the synthetic secretagogues, and the endogenous peptide that occupies it, ghrelin, was found afterwards — which is why the receptor is now more often called the ghrelin receptor ^[10].

Activating that receptor releases growth hormone by a route parallel to the growth hormone-releasing hormone route rather than through it. The clearest demonstration of that separation is an interaction study in healthy men: hexarelin alone produced a larger growth hormone response than growth hormone-releasing hormone alone, giving the two together produced a response larger than either, and an infusion of somatostatin that abolished the response to growth hormone-releasing hormone only blunted the response to hexarelin ^[3]. Two stimuli that are additive, and that respond differently to the same inhibitor, are not acting through one pathway.

The second receptor is entirely separate. CD36 is a scavenger receptor expressed in cardiomyocytes and microvascular endothelial cells, best known for the endocytosis of oxidised low-density lipoprotein by macrophages. It binds hexarelin, and it does not release growth hormone. That interaction is described in the mechanism section below and in the preclinical section; it is the reason cardiac findings in this literature cannot be read as downstream consequences of growth hormone release.

Hexarelin Mechanism of Action

In vitro research

The CD36 interaction was established by working backwards from binding. Rat cardiac membranes were labelled with a radioactive photoactivatable derivative of hexarelin and the labelled protein purified by lectin affinity chromatography and preparative gel electrophoresis; the binding protein that came out had a relative molecular mass of 84,000, and N-terminal sequencing of the deglycosylated protein identified it as rat CD36 ^[10].

A later photoaffinity cross-linking study narrowed the binding site within the receptor. Covalent photolabelling followed by enzymatic and chemical degradation of the ligand-receptor complex produced an 8 kDa labelled fragment corresponding to CD36 residues Asn132 to Glu177, and chemical cleavage with cyanogen bromide released the free ligand — which places Met169 as the contact point inside the binding pocket. The authors note that this domain overlaps the region of CD36 that binds oxidised low-density lipoprotein, residues Gln155 to Lys183 ^[11].

That overlap is the mechanistic claim worth keeping: it predicts that the peptide and a modified lipoprotein compete for the same surface on the same receptor. It is a structural result about two ligands and one protein, established in cell-free and cell-based systems, and it says nothing about what happens in an intact organism.

What Is Hexarelin Being Researched For?

The published record divides into three lines, and they are not equally developed.

• Provocative testing of pituitary growth hormone reserve. The largest and best-characterised line. The compound was compared against growth hormone-releasing hormone in healthy adults and children and against insulin-induced hypoglycaemia in patients with pituitary disease ^{[1, 4, 8]}.
• Growth hormone secretagogue pharmacology in humans. Route of administration, the relationship between the amount administered and the response, interaction with growth hormone-releasing hormone and somatostatin, and what happens to the response when administration continues for weeks ^{[2, 3, 6, 5]}.
• Cardiac and vascular CD36 biology. Entirely preclinical, in rats and in genetically modified mice ^{[9, 10]}.

There is no registered clinical programme in any indication, no approval anywhere that this page can verify, and no human cardiac literature for this compound. Where a human question has been answered it was answered in the 1990s, in studies of pharmaceutical investigational material administered under a protocol.

Human Research on Hexarelin

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Four routes of administration in healthy volunteers

Population. Twelve healthy young volunteers, each receiving the compound intravenously, subcutaneously, intranasally and orally, with intravenous saline and growth hormone-releasing hormone as reference treatments ^[1].

Result. Intravenous administration at 1 µg/kg produced a growth hormone release roughly twice that of growth hormone-releasing hormone at 1 µg/kg (area under the curve 3175 ± 506 against 1544 ± 161 µg·min/L, p < 0.001). The response graded with the amount administered by both the intravenous and subcutaneous routes, and the intravenous response was reproducible on repeat testing. Biological bioavailability was 77.0 ± 10.5% subcutaneously, 4.8 ± 0.9% intranasally and 0.3 ± 0.1% orally ^[1].

Why it matters. The three-order-of-magnitude spread in bioavailability across routes is the single most quoted fact about this compound, and it is measured rather than inferred.

Rising-amount study in healthy men

Population. Twelve adult male volunteers in a double-blind, placebo-controlled, rising-amount study of single intravenous boluses ^[2].

Result. Plasma growth hormone rose with the amount administered, peaked near 30 minutes and returned to baseline within 240 minutes, with a half-life of approximately 55 minutes. Mean peak concentrations were 3.9, 26.9, 52.3 and 55.0 ng/mL for placebo and the three ascending amounts. Logistic regression put the half-maximal amount at 0.50–0.64 µg/kg, meaning the response at 2 µg/kg was already close to maximal ^[2].

Children and hypopituitary subjects

Population. 45 short normal children, 10 prepubertal children with obesity, and 5 subjects with organic hypopituitarism ^[4].

Result. In every short normal child the compound produced a prompt rise in serum growth hormone, peaking 15–30 minutes after injection, significantly greater than the response to growth hormone-releasing hormone and independent of sex and pubertal stage. In the hypopituitary subjects neither stimulus produced any growth hormone rise. In the children with obesity both responses were lower than in the prepubertal comparison group, and the response to hexarelin remained the larger of the two. In the short normal and obese children, but not the hypopituitary subjects, cortisol and prolactin rose slightly and returned to baseline within two hours. No adverse effects were reported ^[4].

Limitations. A single-administration diagnostic comparison, not a treatment study.

Against the reference standard in pituitary disease

Population. 19 patients with possible pituitary disease, each tested with both insulin-induced hypoglycaemia — the reference standard for growth hormone and cortisol deficiency — and hexarelin at 2 µg/kg ^[8].

Result. Peak growth hormone was significantly higher after hexarelin than after hypoglycaemia (67.1 ± 16 against 26.9 ± 6.8 mU/L, p < 0.001), while peak cortisol was significantly lower (420 ± 34 against 605 ± 50 nmol/L, p < 0.001). Peak responses correlated between the two tests, and peak growth hormone after either test correlated with insulin-like growth factor 1. Every patient with a subnormal growth hormone response to hexarelin also had a subnormal response to the insulin tolerance test ^[8].

Limitations. Nineteen patients at one centre, and a test that reads differently for the two hormones — more sensitive for growth hormone, less so for cortisol.

Sixteen weeks of repeated administration

Population. Adults receiving twice-daily subcutaneous administration at 1.5 µg/kg for 16 weeks, with the growth hormone response to a fixed challenge measured at weeks 0, 1, 4, 16 and 20 ^[6].

Result. The area under the growth hormone curve fell from 19.1 ± 2.4 µg/L·h at baseline to 12.3 ± 2.4 at week 4 and 10.5 ± 1.8 at week 16, both significantly below baseline, then rose to 19.4 ± 3.7 four weeks after administration ceased — not significantly different from where it started. Serum insulin-like growth factor 1 and insulin-like growth factor binding protein 3 did not change significantly across the 20 weeks. Of the bone markers measured, only the C-terminal propeptide of type I collagen changed. Total body fat, lean body mass and bone mineral density were unchanged at week 16 ^[6].

Why it matters. Attenuation of the acute response was partial and reversible, and the axis marker that would indicate a sustained biological consequence — insulin-like growth factor 1 — did not move. The authors' own summary is that the biological impact of this schedule on the growth hormone axis appeared minimal. A shorter study in elderly subjects, eight days intranasally and fifteen days orally, found no attenuation of the acute response at all ^[5].

The adrenal axis

Population. 15 healthy young male volunteers, given hexarelin, corticotropin-releasing hormone or desmopressin alone and in combination ^[7].

Result. Hexarelin significantly increased adrenocorticotropic hormone and cortisol release. Adding corticotropin-releasing hormone at a maximally stimulating amount augmented that release further, whereas adding desmopressin did not. Growth hormone and prolactin also rose and were unaffected by either co-administration. Visual analogue scales recorded a small acute increment in appetite ^[7]. The authors concluded that the adrenal effect does not proceed through corticotropin-releasing hormone and may involve arginine vasopressin release instead.

A separate study of nocturnal administration in healthy volunteers reported that the compound reduced slow-wave sleep while stimulating growth hormone, adrenocorticotropic hormone, cortisol and prolactin secretion during sleep ^[12].

Why it matters. A secretagogue that moves the adrenal axis as well as the somatotropic axis is not a clean single-hormone probe, and both of the studies above were designed to establish exactly that.

Preclinical Research on Hexarelin

Animal research

The cardiac line began with an observation that had nothing to do with receptors: inducing selective growth hormone deficiency in rats made cardiac dysfunction after experimental ischaemia and reperfusion worse, and short-term administration of hexarelin reversed that, as did growth hormone itself. The question was whether the peptide was simply acting as a growth hormone delivery mechanism.

It was not. In hypophysectomised rats — animals with no pituitary and therefore no secretagogue-driven growth hormone release — seven days of subcutaneous hexarelin at 80 µg/kg prevented the worsening of ischaemia-reperfusion damage caused by hypophysectomy. It prevented rises in left ventricular end-diastolic pressure, coronary perfusion pressure, coronary reactivity to angiotensin II and creatine kinase release into the perfusate, prevented the fall in prostacyclin release, and improved the return of contractility. Growth hormone at 400 µg/kg produced similar results. A second growth hormone-releasing peptide, EP 51389, which does not bind to the heart, produced none ^[9].

The internal control in that experiment is what makes it worth reporting: a structurally related secretagogue that lacks cardiac binding also lacks the cardiac effect, in the same model, in the same laboratory.

The receptor behind it was identified three years later. In perfused hearts, hexarelin raised coronary perfusion pressure in proportion to the amount applied; the response was absent in hearts from CD36-null mice and from spontaneously hypertensive rats that are genetically CD36-deficient, and its magnitude tracked CD36 expression measured by immunoblotting ^[10].

Findings described in this section were observed in animals, and nothing in them establishes anything about humans. There is no human cardiac literature for this compound.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Hexarelin vs Related Compounds

The comparisons below are structural, pharmacological and evidential. No comparison of effect is made on this page.

Structure

GHRP-6 is His-D-Trp-Ala-Trp-D-Phe-Lys-NH₂; hexarelin is the same chain with a 2-methyl group on the D-tryptophan. GHRP-2 replaces two residues rather than modifying one. Ipamorelin is a pentapeptide built on a different scaffold.

Receptor breadth

All four act at GHS-R1a. Hexarelin is the member of the series whose second receptor, CD36, has been mapped to a specific binding domain ^[11]. Ipamorelin was selected for the opposite property — a narrow profile, without the adrenal axis activation that hexarelin shows in humans ^[7].

Mechanistic class

Sermorelin and tesamorelin are growth hormone-releasing hormone analogues and act at a different receptor entirely. The additive interaction between the two classes is a measured result, not an assumption ^[3].

Evidence base

Tesamorelin has an approved product and phase 3 trials; GHRP-2 has an approved diagnostic use in Japan. Hexarelin has a substantial human clinical pharmacology literature from one decade, no registrational programme, and no approval.

Chemical & Molecular Characteristics

Hexarelin is a small, fully synthetic, chemically modified peptide, and its register record is complete in a way that larger recombinant proteins in this library are not.

The sequence cannot be written in single-letter code. Position two is 2-methyl-D-tryptophan, a non-proteinogenic residue with no single-letter representation, and positions two and five are D-enantiomers. The three-letter string His-D-2-Me-Trp-Ala-Trp-D-Phe-Lys-NH₂ is therefore the shortest complete statement of the covalent structure, and the trailing amide is part of it rather than a notation convenience.

The identifiers agree. PubChem carries the compound under identifier 6918297 with molecular formula C47H58N12O6 and an average mass of 887.0 g/mol, together with CAS registry number 140703-51-1 and the FDA/NCATS unique ingredient identifier 09QF37C617 under the International Nonproprietary Name examorelin. The records are consistent with each other, which is not true of every compound in this library.

The salt form matters to the number. Material of this class is commonly supplied as an acetate salt. The molecular weight above is the free base; a salt has a different one, and the certificate of analysis for a given lot is the record for that lot.

Two development codes circulate. EP-23905 and MF-6003 both refer to this compound in the older literature, alongside the name examorelin. All four names appear in the same body of work.

Frequently Asked Questions

Scientific References

1. Ghigo E, Arvat E, Gianotti L, et al.. Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man The Journal of clinical endocrinology and metabolism; 1994. PMID 8126144 doi:10.1210/jcem.78.3.8126144
2. Imbimbo BP, Mant T, Edwards M, et al.. Growth hormone-releasing activity of hexarelin in humans. A dose-response study European journal of clinical pharmacology; 1994. PMID 7957536 doi:10.1007/BF00191904
3. Arvat E, Gianotti L, Di Vito L, et al.. Modulation of growth hormone-releasing activity of hexarelin in man Neuroendocrinology; 1995. PMID 7731498 doi:10.1159/000126827
4. Loche S, Cambiaso P, Carta D, et al.. The growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, in short normal and obese children and in hypopituitary subjects The Journal of clinical endocrinology and metabolism; 1995. PMID 7852535 doi:10.1210/jcem.80.2.7852535
5. Ghigo E, Arvat E, Gianotti L, et al.. Short-term administration of intranasal or oral Hexarelin, a synthetic hexapeptide, does not desensitize the growth hormone responsiveness in human aging European journal of endocrinology; 1996. PMID 8921821 doi:10.1530/eje.0.1350407
6. Rahim A, O'Neill PA, Shalet SM. Growth hormone status during long-term hexarelin therapy The Journal of clinical endocrinology and metabolism; 1998. PMID 9589671 doi:10.1210/jcem.83.5.4812
7. Korbonits M, Kaltsas G, Perry LA, et al.. The growth hormone secretagogue hexarelin stimulates the hypothalamo-pituitary-adrenal axis via arginine vasopressin The Journal of clinical endocrinology and metabolism; 1999. PMID 10404825 doi:10.1210/jcem.84.7.5811
8. Korbonits M, Kaltsas G, Perry LA, et al.. Hexarelin as a test of pituitary reserve in patients with pituitary disease Clinical endocrinology; 1999. PMID 10469018 doi:10.1046/j.1365-2265.1999.00828.x
9. Locatelli V, Rossoni G, Schweiger F, et al.. Growth hormone-independent cardioprotective effects of hexarelin in the rat Endocrinology; 1999. PMID 10465272 doi:10.1210/endo.140.9.6948
10. Bodart V, Febbraio M, Demers A, et al.. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart Circulation research; 2002. PMID 11988484 doi:10.1161/01.res.0000016164.02525.b4
11. Demers A, McNicoll N, Febbraio M, et al.. Identification of the growth hormone-releasing peptide binding site in CD36: a photoaffinity cross-linking study The Biochemical journal; 2004. PMID 15176951 doi:10.1042/BJ20040036
12. Frieboes RM, Antonijevic IA, Held K, et al.. Hexarelin decreases slow-wave sleep and stimulates the secretion of GH, ACTH, cortisol and prolactin during sleep in healthy volunteers Psychoneuroendocrinology; 2004. PMID 15177700 doi:10.1016/S0306-4530(03)00152-5

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Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.