Hexarelin

Overview

Hexarelin is a synthetic hexapeptide growth hormone secretagogue developed in Italy in the early 1990s. It belongs to the same family as GHRP-6, GHRP-2 and Ipamorelin, and is chemically the closest of them to GHRP-6.

It is not part of our catalogue. It is documented because it is the member of this family with a genuinely separate pharmacology, and the group is easier to understand complete.

Chemical identity

• Also known as: examorelin
• Sequence: His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂
• CAS number: 140703-51-1
• Molecular formula: C₄₇H₅₈N₁₂O₆
• Molecular weight: 887.0 g/mol
• Classification: Growth hormone secretagogue, GHS-R1a agonist
• Length: 6 residues, C-terminally amidated

One methyl group from GHRP-6

The relationship is exact and visible in the formulae:

• GHRP-6: C₄₆H₅₆N₁₂O₆ — 873.0 g/mol
• Hexarelin: C₄₇H₅₈N₁₂O₆ — 887.0 g/mol

One carbon and two hydrogens: a single CH₂, worth exactly 14 g/mol. The sequences are otherwise identical, and the addition sits on the D-tryptophan at position 2, making it D-2-methyl-tryptophan.

Methylating that indole ring increases metabolic stability and receptor affinity. It is among the smallest modifications in this library that produces a compound with its own name and its own literature — a useful reminder of how little change is needed when the change is in the right place.

The second receptor

This is what separates hexarelin from the rest of its class.

All four secretagogues here agonise GHS-R1a, the ghrelin receptor, and release growth hormone through it. Hexarelin also binds CD36 — a scavenger receptor expressed in cardiac tissue, macrophages and elsewhere, with no relationship to the growth hormone axis at all.

The consequence is that hexarelin has reported cardiovascular effects that are not mediated by growth hormone. Published work has examined cardioprotective effects in animal models under conditions where the growth hormone pathway was absent or blocked, and reported that the effects persisted. That is the experiment that matters: if an effect survives removal of the presumed mechanism, the presumed mechanism is not the whole story.

For research purposes this cuts both ways. It makes hexarelin a tool for studying CD36 biology and cardiac effects independent of the somatotropic axis. It also makes it a poor choice where growth hormone release is the variable of interest, because a second active pathway is a confound rather than a bonus.

The secretagogue family, complete

With this compound the four documented here can be compared directly:

• GHRP-6 — 873.0 g/mol. Strongest appetite response. Useful when feeding behaviour is the endpoint.
• GHRP-2 — 818.0 g/mol. Most potent GH release per unit mass; the most formally characterised.
• Ipamorelin — 711.9 g/mol. Cleanest endocrine profile, least effect on other pituitary hormones.
• Hexarelin — 887.0 g/mol. A second receptor and cardiac effects independent of growth hormone.

Four compounds, one primary receptor, four different secondary characteristics. Which is appropriate depends entirely on what is being measured and what would count as a confound.

Mechanism of action

At GHS-R1a, hexarelin behaves as the others do: phospholipase C signalling, calcium release, growth hormone secretion from pituitary somatotrophs, and reduced somatostatin tone. The receptor’s history — characterised before its natural ligand was known — is covered on the GHRP-6 page.

At CD36 the pharmacology is different in kind. CD36 is a scavenger receptor involved in fatty acid transport and lipoprotein handling rather than a classical signalling GPCR, and the mechanism by which a hexapeptide engaging it produces cardiac effects is less well defined than the growth hormone pathway.

Handling and storage

• Two tryptophans, as with GHRP-6 — one methylated, one not. Light protection matters here for the same reason: indole is the most photosensitive amino acid side chain, and a third of this sequence carries one.
• No methionine or cysteine, so oxidation of those residues is not a concern.
• Lyophilised storage: sealed, refrigerated, protected from light; freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall and allow to dissolve undisturbed.

Purity and analytical verification

The verification question here is unusually clean, and it follows directly from the relationship to GHRP-6.

The two compounds differ by 14 g/mol. A synthesis using ordinary D-tryptophan in place of the methylated form — a cheaper and more readily available reagent — would produce GHRP-6, at 873 rather than 887. That is a clear separation at this molecular weight and unambiguous on any competent instrument.

So a mass figure consistent with 887 confirms the methylation is present. It is worth asking for specifically, because the substitution is economically tempting, the resulting compound is still an active secretagogue, and a purity assay would report the substituted material as perfectly pure — pure GHRP-6, sold as hexarelin.

That is a recurring theme across this library: purity and identity are different questions, and a certificate that answers only the first can be entirely accurate about the wrong molecule.

References

• Deghenghi R, Cananzi MM, Torsello A, et al. GH-releasing activity of hexarelin, a new growth hormone releasing peptide, in infant and adult rats. Life Sciences, 1994. PMID 7910650
• 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
• Locatelli V, Rossoni G, Schweiger F, et al. Growth hormone-independent cardioprotective effects of hexarelin in the rat. Endocrinology, 1999. PMID 10465272

Summary

Hexarelin (examorelin) is a synthetic hexapeptide growth hormone secretagogue, His-D-2-methyl-Trp-Ala-Trp-D-Phe-Lys-NH₂, CAS 140703-51-1, molecular formula C₄₇H₅₈N₁₂O₆, molecular weight 887.0 g/mol. It is GHRP-6 with a single methyl group added to the tryptophan at position 2, worth 14 g/mol. Beyond the ghrelin receptor it also binds CD36, a scavenger receptor in cardiac tissue unrelated to the growth hormone axis, and reported cardioprotective effects persist when growth hormone signalling is removed. That second pathway makes it a distinct research tool and a poor choice where growth hormone release is the variable being measured. We do not stock it.

This page is provided for research reference. Compounds described in this library are for laboratory research use only, are not drugs, foods or cosmetics, and may not be used for any purpose other than in vitro or non-human laboratory research.