GHRP-6 is the original growth hormone-releasing hexapeptide, sequence His-D-Trp-Ala-Trp-D-Phe-Lys-NH2, and the tool compound whose behaviour led directly to the discovery of the growth hormone secretagogue receptor GHS-R1a in 1996 and of its endogenous ligand ghrelin in 1999. Every other peptide in this class — GHRP-2, hexarelin, ipamorelin — is a refinement of the scaffold that GHRP-6 established. It is also the member of the class with the most pronounced effect on food intake in rodent models, which gives it a distinct research role beyond endocrinology.
This page sets out where the sequence came from, what its structural features contribute, the receptor mechanism, the published research areas, and how the material is specified and handled. GHRP-6 is supplied for laboratory research use only.
GHRP-6 at a glance
| Property | Value |
|---|---|
| Sequence | His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 |
| Length | 6 residues, C-terminally amidated |
| Origin of the scaffold | Met-enkephalin analogue work, 1980s |
| CAS number | 87616-84-0 |
| Molecular formula | C46H56N12O6 |
| Molecular weight | 873.01 g/mol |
| Receptor | GHS-R1a (ghrelin receptor), class A GPCR |
| Signalling | Gq → phospholipase C → IP3 / DAG → intracellular calcium |
| Distinctive feature | Most pronounced food-intake effect in rodents among the GHRP series |
| Sizes supplied | 5 mg, 10 mg lyophilized vials |
| Purity specification | ≥99% by RP-HPLC with lot-matched COA |
Origin and structure: the compound that implied a receptor
The story begins with met-enkephalin. In the 1970s and 1980s, Cyril Bowers and colleagues examined opioid peptide analogues and noticed that certain fragments released growth hormone. The critical observation was negative: the effect could not be blocked by GHRH antagonists, and it was not mediated by opioid receptors either. Something else had to be there. GHRP-6 emerged from that structure-activity work as the most useful probe, and for a decade it was the compound used to hunt for a receptor nobody had yet found. The hunt succeeded twice — GHS-R1a was cloned in 1996, and ghrelin was identified as its endogenous ligand in 1999.
Structurally the hexapeptide is built around two aromatic pairs and a stabilising strategy. The D-tryptophan at position 2 and the D-phenylalanine at position 5 place bulky aromatic side chains in a configuration ordinary proteases do not process; the tryptophan at position 4 contributes a second indole; and the C-terminal lysine amide removes the terminal negative charge, a feature conserved across the whole class. The histidine at position 1 is the residue that later analogues replaced — GHRP-2 substitutes D-alanine there — because a free N-terminal L-residue is the obvious point of aminopeptidase attack.
At 873.01 g/mol GHRP-6 is the heaviest of the three secretagogues stocked here, against 817.97 for GHRP-2 and 711.85 for ipamorelin. All three remain far lighter than any GHRH analogue, which is why 5 mg and 10 mg vials go a long way in this class.
How GHRP-6 is thought to work
GHRP-6 is an agonist at GHS-R1a, a class A G protein-coupled receptor expressed on pituitary somatotrophs, in the hypothalamic arcuate nucleus and in peripheral tissue including the gastrointestinal tract. Agonist binding activates Gq, stimulating phospholipase C, generating inositol trisphosphate and diacylglycerol and raising intracellular calcium to trigger secretory granule release. Suppression of somatostatin tone is a second reported contribution, lifting an inhibitory brake at the same time as the stimulatory signal arrives.
Two features distinguish GHRP-6 from its successors in the comparative literature. The first is potency: it is the least potent of the series at releasing growth hormone, which is precisely what the later medicinal chemistry set out to improve. The second is breadth. Alongside growth hormone, published work reports increases in prolactin, ACTH and cortisol, and — the most cited effect — a marked increase in food intake in rodent models, considerably greater than that reported for GHRP-2 and largely absent with ipamorelin. That reflects engagement of arcuate nucleus circuits, notably NPY and AgRP neurons, which is the same pathway ghrelin itself uses.
Read as a whole, GHRP-6 behaves less like a selective endocrine tool and more like a broad ghrelin receptor agonist. For a study isolating somatotroph signalling that is a liability; for a study on ghrelin receptor involvement in feeding circuits, gastric motility or cytoprotection, it is the correct compound and ipamorelin is not. The selectivity contrast is examined in ipamorelin vs GHRP-6.
What research has examined
Receptor discovery and pharmacology
GHRP-6 is the historic reference agonist for GHS-R1a and remains a standard in binding assays, calcium flux and inositol phosphate accumulation work, and in potency ranking across the GHRP class.
Food intake and hypothalamic circuits
Rodent studies have examined food intake, arcuate nucleus neuronal activation and NPY/AgRP signalling, using GHRP-6 as a synthetic surrogate for ghrelin. This is the strand where GHRP-6 is preferred over its more selective successors, because the property that makes it unselective is the property under study.
Gastric motility and gastrointestinal models
Ghrelin receptor agonists are studied in gastric emptying, motility and postoperative ileus models, drawing on the peripheral distribution of the receptor.
Cytoprotection and cardiovascular models
A separate body of preclinical work has examined GHRP-6 in tissue-protection and cardiac models, some of it linked to receptor subtypes other than GHS-R1a, including CD36. This literature is smaller and less settled.
Combination designs
Pairing a secretagogue with a GHRH receptor agonist is a standard design because the two receptors sit on the same cell and use different second messengers; pre-blended research material exists as CJC-1295 with GHRP-6. Both molar concentrations should be reported rather than a combined mass, since the peptides differ in molecular weight by roughly fourfold.
Forms and sizes we supply
GHRP-6 is stocked as a lyophilized powder in 5 mg (USD 50) and 10 mg (USD 80) sealed vials. At 873.01 g/mol a 5 mg vial contains approximately 5.73 micromoles, close to four times the molar content of a 5 mg vial of a GHRH analogue. The class sits under GHRPs and secretagogues, where hexarelin is also stocked as the most potent member of the series.
Reconstitution and storage in a laboratory context
The calculation: a 5 mg vial reconstituted with 2 mL of bacteriostatic water gives 2.5 mg/mL, equivalently 2,500 mcg/mL; 0.1 mL (10 units on a U-100 syringe) contains 250 mcg. In molar terms the stock is approximately 2.86 mM, so an assay concentration of 10 nanomolar requires roughly a 286,000-fold dilution, made in stages.
The dominant handling concern for this peptide is light. GHRP-6 contains two tryptophan residues, one of them in the D configuration, and indole side chains are photosensitive: prolonged light exposure degrades them and generates products that show as additional chromatographic peaks. Protecting powder and solution from light is a specific requirement here rather than a generic precaution. Beyond that the peptide is chemically forgiving, with no cysteine, no methionine and no asparagine. The three aromatic side chains make it less hydrophilic than its size suggests, so allow full dissolution and inspect for clarity before use. Lyophilized vials are stored at −20 °C protected from light and moisture; reconstituted solution is refrigerated and aliquoted. General guidance is in the peptide storage guide.
Purity, COA and how to read one
Each lot is purified by reversed-phase HPLC to at least 99% with mass confirmation and a lot-matched certificate. Three checks apply. First, confirm the mass against 873.01 g/mol for the amidated hexapeptide; a value about 1 Da higher indicates the free acid, which is a different molecule pharmacologically. Second, the class is easy to tell apart by mass — 873.01 for GHRP-6, 817.97 for GHRP-2, 711.85 for ipamorelin — so a mislabelled vial is immediately visible on the certificate. Third, look at the chromatogram with tryptophan degradation in mind: early-eluting shoulders or minor late peaks in a peptide of this composition are worth questioning, since they are the signature of light-driven indole degradation. As always, the D configurations at positions 2 and 5 cannot be confirmed by mass spectrometry, because enantiomers are isobaric. Our COA reading guide explains what each analytical section can and cannot establish.
Regulatory status
GHRP-6 has no marketing authorisation as a medicine in the United States or elsewhere, is not a dietary supplement ingredient, and is not a generally available compounded medication. Material supplied here is research use only, for in-vitro and preclinical laboratory investigation by qualified researchers, and is not intended for human or veterinary administration.
Related peptides and further reading
GHRP-2 is the potency-optimised successor on the same scaffold, hexarelin the most potent member of the series, and ipamorelin the selective modern standard against which the older compounds are measured. On the other arm of the axis, sermorelin, Modified GRF 1-29 and tesamorelin act at the GHRH receptor through cyclic AMP rather than calcium. The whole landscape is mapped in the GH secretagogue landscape explained.