What hexarelin is
Hexarelin is a synthetic peptide of six amino acids belonging to the growth-hormone-releasing-peptide (GHRP) family, a group of small peptides derived from met-enkephalin in the 1980s that stimulate growth-hormone release through a receptor distinct from that of growth-hormone-releasing hormone. Its sequence is His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH2. It is the 2-methyl-tryptophan analogue of GHRP-6, and the methyl group was introduced by Deghenghi and colleagues to improve chemical stability and potency [1].
Three features of the sequence matter for handling and analysis. Two residues are in the D-configuration, which protects against proteolysis. Two residues are tryptophan derivatives, which give the peptide strong absorbance at 280 nm and make it sensitive to light and oxidation. And the C-terminus is amidated. The molecule is a white lyophilised powder in its research presentation.
| Identifier | Value |
|---|---|
| CAS number | 140703-51-1 |
| Sequence | His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2 |
| Molecular formula | C47H58N12O6 |
| Molecular weight | 887.0 g/mol (average) |
| Residues | 6 |
| Non-natural residues | D-2-methyl-tryptophan, D-phenylalanine |
| C-terminus | Amidated |
| Appearance | White lyophilised powder |
| Catalogue sizes | 5 mg |
How the literature describes its mechanism
When the GHRPs were designed, their receptor was unknown. Howard and colleagues cloned it in 1996 as the growth-hormone secretagogue receptor, GHS-R1a, a G-protein-coupled receptor expressed in the pituitary and hypothalamus [2], and Kojima and colleagues identified its endogenous ligand three years later as ghrelin, an acylated 28-residue peptide from the stomach [3]. Hexarelin is therefore best described today as a synthetic ghrelin receptor agonist. Activation of GHS-R1a in pituitary somatotrophs raises intracellular calcium through Gq and phospholipase C, and releases growth hormone by a mechanism that is additive with, and partly dependent on, growth-hormone-releasing hormone.
Hexarelin has a second binding partner that distinguishes it from the rest of the family. Bodart and colleagues showed that it binds CD36, a scavenger receptor on macrophages and cardiomyocytes, and that CD36 mediates the coronary vasoactive effect of GHRPs in isolated perfused hearts [4]. Much of the later preclinical literature on hexarelin concerns this cardiac and vascular pharmacology rather than growth hormone, and a laboratory interested in CD36 signalling has reason to choose hexarelin over ipamorelin or GHRP-2, which lack that activity.
For an in-vitro programme the relevant readouts are calcium mobilisation or inositol phosphate accumulation in cells expressing GHS-R1a, growth-hormone release from pituitary cell cultures, and CD36-dependent responses in macrophages or cardiomyocytes. Like ghrelin itself, hexarelin shows constitutive-activity and desensitisation behaviour at the receptor that should be allowed for in assay design.
The research record
Hexarelin's record is unusual among the research-peptide catalogue in that it includes controlled human studies from the 1990s. Ghigo and colleagues reported that it released growth hormone in healthy adults after intravenous, subcutaneous, intranasal and oral administration, with a dose-dependent response and a potency greater than GHRP-6 [5]. Subsequent studies from the same groups examined its effects in children with short stature, in older adults and in combination with growth-hormone-releasing hormone, and documented the attenuation of the growth-hormone response on repeated administration that is common to the GHRPs. Development as a medicine did not proceed, in part because of that desensitisation and in part because of the arrival of ghrelin receptor agonists with better oral properties.
The preclinical literature after 2000 centres on the heart. Hexarelin was reported to protect against ischaemia–reperfusion injury in rat models, to improve cardiac function in experimental heart failure, and to act on cardiomyocytes through CD36 and through GHS-R1a independently of growth hormone [4, 6]. These remain research findings in animal and cell systems.
Regulatory status in the United Kingdom
Hexarelin has no marketing authorisation in the UK or anywhere else and is not a medicine. It is not controlled under the Misuse of Drugs Act. It is supplied here as a chemical for in-vitro laboratory use under the Terms of Sale, not for human or veterinary administration. Purchasers must be 18 or over and are responsible for compliance with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.
In sport, hexarelin is prohibited at all times. The WADA Prohibited List names it explicitly under S2.2, growth-hormone-releasing factors, as a growth-hormone secretagogue.
Handling, storage and stability
Hexarelin is supplied lyophilised, sealed under nitrogen in a glass vial with a rubber stopper and an aluminium flip-off crimp.
Sealed vial. Store at 2–8 °C for routine use and at −20 °C for storage beyond a few months. Protect from light; the two tryptophan residues are photosensitive, and this is a stricter requirement for hexarelin than for most peptides in the catalogue. Allow a refrigerated vial to reach room temperature before opening.
Reconstitution. Hexarelin is readily soluble in water, bacteriostatic water and common buffers. Add the solvent down the side of the vial and swirl. Dissolution is fast; no lipid chain, no aggregation tendency. The reconstitution calculator gives the volume for a target concentration.
Reconstituted solution. Keep at 2–8 °C in an amber or foil-wrapped tube, and use within a few weeks. The D-residues make the peptide resistant to proteolysis, so stability in solution is good as long as light and oxygen are kept out. Aliquot and freeze at −20 °C if the solution must be kept longer.
Surfaces. A small cationic peptide with two aromatic residues adsorbs modestly to glass and plastic at very low concentrations; this is rarely a problem at working concentrations but worth remembering when preparing nanomolar dilutions. The storage and stability guide covers short peptides in general.
What a sound certificate for hexarelin looks like
Every batch we release carries an independent certificate of analysis, transcribed on the product page and in the certificate register.
Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection. Hexarelin's tryptophan residues make it one of the few peptides in the catalogue for which 280 nm detection is informative, and a certificate may report purity at 214 or 220 nm, at 280 nm, or both. A good batch shows a single dominant peak at 98% or above. The main impurities to look for are the oxidised tryptophan species (+16 Da, eluting slightly earlier) and the diastereomer in which one of the D-residues has racemised, which elutes close to the parent.
Identity by LC-MS. The average molecular weight is 887.0 Da and the monoisotopic mass is 886.5 Da. A peptide of this size usually appears as the singly charged [M+H]⁺ at m/z 887.5 or the doubly charged [M+2H]²⁺ at m/z 444.3; the certificate should say which it reports. The mass alone cannot distinguish hexarelin from a diastereomer, which is why the HPLC profile matters.
Net peptide content. A small basic peptide carries a substantial weight of trifluoroacetate counter-ion, often 10–15% of the powder mass, so net peptide content should be reported where available.
Endotoxin. Where tested, a LAL result in endotoxin units per milligram.
Our guide to reading a certificate of analysis goes through a complete report line by line.
Related compounds
Hexarelin is one of several growth-hormone secretagogues in the catalogue. Ipamorelin is a pentapeptide GHRP with a more selective profile and no CD36 activity. Sermorelin and tesamorelin are analogues of growth-hormone-releasing hormone and act at a different receptor, GHRH-R, which is why the two classes are often studied together. CJC-1295 without DAC is a stabilised GHRH analogue frequently paired with a GHRP.
Frequently asked questions
How does hexarelin differ from GHRP-6? By one methyl group, on the indole ring of the second tryptophan. The change improves stability and potency, and gives hexarelin a distinct CD36-binding activity.
Why is hexarelin sensitive to light? It contains two tryptophan residues, which photo-oxidise. Keep the vial and any solution out of direct light.
Is hexarelin a ghrelin analogue? It is a ghrelin receptor agonist, but it was designed a decade before ghrelin was discovered and shares no sequence with it.
Is it on the WADA list? Yes, named under S2.2 as a growth-hormone secretagogue, prohibited at all times.
References
- Deghenghi R, Cananzi MM, Torsello A, Battisti C, Muller EE, Locatelli V. GH-releasing activity of hexarelin, a new growth hormone releasing peptide, in infant and adult rats. Life Sciences. 1994;54(18):1321–1328. doi:10.1016/0024-3205(94)00510-9.
- Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974–977. doi:10.1126/science.273.5277.974.
- Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. doi:10.1038/45230.
- Bodart V, Febbraio M, Demers A, et al. CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart. Circulation Research. 2002;90(8):844–849. doi:10.1161/01.RES.0000016164.02525.B4.
- 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. Journal of Clinical Endocrinology & Metabolism. 1994;78(3):693–698. doi:10.1210/jcem.78.3.8126144.
- Mao Y, Tokudome T, Kishimoto I. The cardiovascular action of hexarelin. Journal of Geriatric Cardiology. 2014;11(3):253–258. doi:10.3969/j.issn.1671-5411.2014.03.007.
This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.