Key Takeaways
- •Hexarelin is a synthetic hexapeptide, sequence His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2, and a full agonist at the growth hormone secretagogue receptor GHS-R1a.
- •It differs from GHRP-6, from which it derives, by methylation at position 2 of the D-tryptophan. Molecular weight is around 887 Da.
- •It also binds CD36, a scavenger receptor unrelated to GHS-R1a. Bodart et al. (2002) identified that binding protein in rat cardiac membranes by photoaffinity labelling (PMID 11988484).
- •Functional responses attributed to that site were absent in tissue from CD36-null mice, which is what ties them to CD36 rather than to GHS-R1a.
- •Continuous exposure produces tachyphylaxis, attributed to GHS-R1a internalisation, and in animal work the response recovers after exposure stops.
- •No regulator has approved hexarelin for any use.
Summary
Hexarelin is a six amino acid synthetic peptide that activates the ghrelin receptor GHS-R1a, a G-protein-coupled receptor expressed in pituitary somatotroph cells, the hypothalamus and peripheral tissues. On somatotrophs, GHS-R1a activation is the trigger for growth hormone release, which is why hexarelin is classed as a growth hormone secretagogue.
The more unusual pharmacology is a second binding site. In heart tissue hexarelin binds CD36, a scavenger receptor and fatty acid transporter, rather than GHS-R1a, and the evidence for that comes from photoaffinity labelling plus knockout controls rather than from inference.
The receptor-level complication is desensitisation. Continuous agonist exposure drives GHS-R1a internalisation and the response falls; in animal work it recovers once exposure stops.
Structure and Classification
Hexarelin, also known as Examorelin or EP-23905, is a synthetic hexapeptide and agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a). It was created at Europeptides in Italy in the early 1990s, with detailed characterisation by Ghigo, Arvat and colleagues at the University of Turin, and it has served as a reference compound in GHS-R1a pharmacology since.
Its amino acid sequence is His-D-2-MeTrp-Ala-Trp-D-Phe-Lys-NH2. Two residues are D-amino acids and the C-terminus is amidated, both features that resist proteolysis. The methylation at position 2 of the tryptophan sets it apart from GHRP-6, the ghrelin mimetic from which it derives. With six residues and a molecular weight around 887 Da, it is stable as a lyophilised solid under typical laboratory storage. Because two of its residues are D-isomers, a matching mass does not establish correct stereochemistry; see what proves a sequence. The Peptide Glossary defines the terms used here.
GHS-R1a: The Primary Receptor
GHS-R1a is a G-protein-coupled receptor whose endogenous ligand is ghrelin. It is expressed in the anterior pituitary, the hypothalamus and several peripheral tissues. In pituitary somatotroph cells its activation initiates a G-protein cascade that ends in growth hormone exocytosis.
Hexarelin binds the receptor as a non-natural full agonist. Its activity is additive with GHRH, which acts through a separate pituitary receptor and a separate signalling route, so the two are used together in studies of how the two receptor systems interact.
GHS-R1a also has high constitutive activity: it signals at a measurable level with no ligand bound. A full agonist drives the receptor above that baseline.
Ghigo et al. (1994, PMID 8126144) is the human pharmacology study most often cited for hexarelin, measuring growth hormone response against GHRH as the comparator. Its figures are not reproduced here. Note what its comparator was: hexarelin against GHRH, not against GHRP-6 or GHRP-2, so it does not support the frequently repeated ranking of hexarelin as the strongest compound in its class.
CD36: The Second Binding Site
Bodart et al. (2002) identified the cardiac hexarelin binding protein as CD36, separate from GHS-R1a, by labelling rat cardiac membranes with a photoactivatable hexarelin derivative (PMID 11988484). Functional responses to hexarelin in perfused hearts were absent in hearts from CD36-null mice, which is the control that assigns them to CD36.
CD36 is a class B scavenger receptor that binds and transports long-chain fatty acids and oxidised lipoproteins. Further work links CD36 engagement to PI3K/Akt and ERK signalling. A second binding site outside GHS-R1a is unusual among GHRP compounds and is the main reason hexarelin is still used in receptor research alongside newer selective agonists.
Locatelli et al. (1999, PMID 10465272) used hypophysectomised rats, which cannot secrete growth hormone, as a model for separating GHS-R1a-pituitary effects from effects that do not run through growth hormone at all. That design question, which receptor carries an observation, is separate from the binding identification in Bodart et al., and the two papers are often merged into one claim.
Comparison With GHRP-6 and GHRP-2
All three share GHS-R1a agonism and differ in structure and in receptor selectivity. GHRP-6 was the first systematically studied compound of the class. GHRP-2 is a later analogue with higher reported receptor potency. Hexarelin is the only one of the three for which a distinct non-GHS-R1a binding site, CD36, has been identified by direct labelling. No head-to-head study comparing all three on a single receptor assay is cited here, so the order in which they are often ranked should be treated as unsupported.
Tachyphylaxis and Receptor Internalisation
Tachyphylaxis, a decline in response with repeated or continuous agonist exposure, is a receptor-level phenomenon here. Sustained GHS-R1a activation drives receptor internalisation and limits how quickly surface receptor is restored. Hexarelin is reported to desensitise faster than GHRP-2. In animal studies the response recovers after exposure stops, indicating that the change is reversible.
Where the Evidence Stands
Hexarelin's pharmacology rests on two findings: full agonism at GHS-R1a, and a separate binding site at CD36 identified by Bodart et al. (2002) with knockout controls. The CD36 work is rat and mouse tissue. Receptor desensitisation through internalisation is the main constraint on how its receptor activity can be studied.
No regulator has approved hexarelin for any use. It is supplied for laboratory research only, to qualified researchers and licensed laboratories, and is not for human consumption. You can find free research tools here.
Related Research Compounds
Every compound below is held to a >99% HPLC purity specification, which is a release threshold rather than a measurement. Published certificates for specific lots are listed on the certificates page, and a certificate for any other batch is available on request.
| Compound | Purity specification | Size |
|---|---|---|
| Ipamorelin 10mg | >99% | 10mg |
| CJC-1295 No DAC + Ipamorelin 10mg (5+5) | >99% | 10mg |
| CJC-1295 DAC 5mg | >99% | 5mg |
| CJC-1295 No DAC 10mg | >99% | 10mg |
