Hexarelin

What Is Hexarelin?

Hexarelin is a synthetic hexapeptide in the growth hormone-releasing peptide (GHRP) family that stimulates growth hormone release and also acts directly on the heart. It binds to and activates the growth hormone secretagogue receptor (GHSR) in the brain, much like its natural counterpart ghrelin.^[1]

Hexarelin was one of the newer GHRP hexapeptides synthesized after GHRP-6 for human studies, alongside GHRP-2 and the heptapeptide GHRP-1.^[2] Researchers describe it as a GHRP-6 analog.^[3] Receptor-binding work has identified GHRP receptor subtypes in the pituitary gland, the hypothalamus and other brain regions, as well as in several peripheral tissues.^[4]

Its research profile is unusual for a growth hormone secretagogue. Alongside endocrine work, a substantial literature examines effects on the cardiovascular system that appear independent of growth hormone, and newer animal studies explore kidney protection.^[5][4][6] Compared with ghrelin, hexarelin has been described as chemically more stable and functionally more potent.^[1]

Chemical Structure and Molecular Identity

Hexarelin is the hexapeptide His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2, identical to GHRP-6 except for a methyl group on the indole ring of the D-tryptophan at position 2. PubChem lists it under CID 6918297 with the molecular formula C47H58N12O6 and a molecular weight of 887.0 g/mol.

The international nonproprietary name is examorelin, and the systematic name is L-histidyl-2-methyl-D-tryptophyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide. Two of the six residues are D-configured, and the 2-methyltryptophan is not a standard proteinogenic amino acid.

Key identifiers

• CAS numbers listed in PubChem: 140703-51-1 and 208251-52-9
• InChIKey: RVWNMGKSNGWLOL-GIIHNPQRSA-N
• Synonyms: examorelin, EP-23905, MF-6003

Because the methyl group is the only change from GHRP-6, the two peptides differ by one carbon and two hydrogens, a molecular weight difference of 14 g/mol (887.0 versus 873.0 g/mol). The added methyl sits on the indole ring that GHRP-6 also carries at position 2.

A radiolabeled extended analog, ¹²⁵I-Tyr-Ala-hexarelin, has served as a research tool for mapping GHRP binding sites in brain, pituitary and peripheral tissues.^[4]

Research History and Development

Hexarelin emerged in the 1990s as part of a series of synthetic hepta- and hexapeptides that proved effective growth hormone releasers in animals and humans. The series included GHRP-1, GHRP-2, GHRP-6 and hexarelin, and GHRP-6 later served as the template for non-peptide secretagogues such as MK-0677.^[7]

At the time, investigators knew that GHRPs act through a receptor distinct from the GHRH receptor, cloned in the 1990s with no sequence homology to other known G-protein-coupled receptors. They inferred that a natural GHRP-like ligand existed but had not yet been found.^[7][2]

Early mechanistic work examined how hexarelin releases growth hormone, including sheep studies of hypothalamic portal blood and cell-line experiments.^[8][3] By 2000, receptor-binding studies had shown GHRP binding sites in the heart and other peripheral tissues, shifting attention toward cardiovascular research.^[4] Later reviews identified CD36 as a specific cardiac receptor for hexarelin and discussed its possible relevance to diabetic heart disease.^[1][5]

Mechanisms Studied in Research

Hexarelin acts through two receptor systems: the growth hormone secretagogue receptor, which drives growth hormone release, and CD36, a non-GHSR receptor in heart tissue linked to its cardioprotective effects.^[1]

Growth hormone release

• Hypothalamic action: in conscious sheep, hexarelin raised jugular growth hormone within 15 minutes and increased GHRH in hypophysial portal blood (145.4 versus 59.2 pg/mL) without changing somatostatin, indicating activation of GHRH neurons in addition to direct pituitary effects.^[8]
• Direct pituitary action: hexarelin stimulated growth hormone release from GH1 rat tumor cells that do not respond to GHRH, and in normal rat pituitary cells its effect added to that of GHRH, suggesting distinct sites and modes of action.^[3]
• Class features: GHRP activity is synergistic with GHRH, is not affected by opioid receptor antagonists, is similar in both sexes, and varies with age, rising from birth to puberty and declining with aging. Reviews propose a dual site of action on pituitary and hypothalamus, possibly involving regulatory factors beyond GHRH and somatostatin.^[7]

Effects beyond growth hormone

GHRPs also release prolactin and ACTH/cortisol and influence food intake and sleep.^[4] In macrophages and adipocytes, hexarelin has been reported to regulate peroxisome proliferator-activated receptor gamma (PPAR-γ), a regulator of fat metabolism and insulin sensitivity.^[5] In a kidney cell model, molecular docking suggested binding to MDM2, pointing to an MDM2/p53 pathway.^[6]

Key Findings From Published Studies

Published studies report that hexarelin binds heart tissue densely, protects heart and kidney tissue in animal ischemia models, and increases cardiac contractility in small human studies. Much of this evidence is summarized in reviews.

Growth hormone release in cells and sheep

In vitro, hexarelin raised growth hormone release to 155% of control in GHRH-insensitive GH1 cells and 185% in normal rat pituitary cells at the highest concentration tested, while the cyclic AMP analog 8Br-cAMP stimulated both cell types.^[3] In six conscious rams, jugular growth hormone rose from 3.9 to 9.1 ng/mL after hexarelin.^[8]

Receptor binding in human tissue

GHRP binding sites were found in heart, adrenal, ovary, testis, lung and skeletal muscle at densities higher than in the hypothalamic-pituitary system. In the human cardiovascular system, binding was highest in the ventricles, followed by atria, aorta and coronary arteries. Hexarelin, GHRP-6, GHRP-1 and GHRP-2 displaced the radioligand from cardiac membranes, but the non-peptide MK-677 did not.^[4]

Cardiovascular findings

• Cell studies: hexarelin showed anti-apoptotic activity in H9c2 cardiomyocyte-derived cells.^[4]
• Animal studies: hexarelin protected against ischemia-induced myocardial damage in aged and growth hormone-deficient rats.^[4]
• Human studies: hexarelin produced a positive inotropic effect in healthy subjects and in patients with growth hormone deficiency.^[4]

Kidney findings

In a rat model of ischemia-reperfusion acute kidney injury, pretreatment with hexarelin reduced tubular damage, improved renal function and inhibited apoptosis, with lower Caspase-3, Bax and Bad and higher Bcl-2. Hexarelin also reduced apoptosis in HK-2 kidney cells after hypoxia-reoxygenation.^[6]

Metabolic research

A 2015 review proposed that ghrelin and hexarelin may be relevant to diabetes and diabetic cardiomyopathy, based largely on cell and animal data.^[5]

Because hexarelin differs from GHRP-6 by a single methyl group, researchers typically confirm identity with mass spectrometry and HPLC data on a certificate of analysis.

Regulatory and Research Status

Hexarelin is not approved by the US Food and Drug Administration for any use and remains an investigational research compound. Growth hormone secretagogues, including hexarelin, are also prohibited in sport under the World Anti-Doping Agency’s Prohibited List.

A 2026 clinical review grouped hexarelin with GHRP-2, GHRP-6 and ipamorelin among unregulated peptides marketed as research compounds to modulate the growth hormone-IGF-1 axis. It noted the absence of regulatory approval for physique or performance indications and uncertainty about product composition in unregulated supply chains.^[9]

Across this peptide group, the review listed reported adverse effects including prolactin and cortisol elevations, appetite changes, dysglycemia, fluid retention and musculoskeletal symptoms.^[9] The review stratified these peptides into evidence tiers, ranging from regulatory-grade randomized trial data to a complete absence of human studies, and highlighted uncertainty around putative performance and body-composition benefits.^[9]

Most mechanistic and protective findings for hexarelin come from cell and animal models, and controlled human outcome trials are lacking.