Molecule guides
GHRP-2 (Pralmorelin): Sequence, GHS-R1a Signalling and Research Applications
The second-generation hexapeptide that helped prove GHS-R1a existed — what each substitution contributes, why it is not selective, and how to verify a vial before use.
Sold under the alternative name pralmorelin, GHRP-2 is a six-residue synthetic agonist of GHS-R1a whose chain reads D-Ala, D-2-Nal, Ala, Trp, D-Phe and amidated Lys. It represents the second generation built on the GHRP-6 template, where installing D-2-naphthylalanine in the second position lifted potency considerably. The compound occupies a particular niche in the history of this field: long before ghrelin was known to be the body's own ligand, GHRP-2 formed part of the evidence that somatotrophs carried a receptor other than the one GHRH uses. Uniquely in its class, it also carries a regulatory clearance — Japanese authorities licensed it for diagnostic measurement of GH output.
What follows: the chemistry residue by residue, the signalling route, the studies that use it, and the specification and bench handling of the material itself.
A second-generation hexapeptide: origin and structure
This family of secretagogues traces back to experiments on met-enkephalin derivatives carried out during the 1980s, out of which came GHRP-6 with its His, D-Trp, Ala, Trp, D-Phe, amidated Lys arrangement. Since blocking the GHRH receptor failed to stop these opioid-derived fragments from eliciting GH, an as-yet-unknown receptor had to be responsible; subsequent chemistry set out to make the same six-residue frame more potent.
GHRP-2 came out of that work, differing from its predecessor at two positions. The second residue exchanges an indole for a naphthalene system — a fused two-ring aromatic that is both larger and less polar, and the principal reason the molecule binds more strongly. The first residue exchanges histidine for D-alanine, dropping the imidazole group and, more to the point, presenting a mirror-image residue to the peptidases that trim from that end. Residues three through six carry over unchanged, and GHRP-6 and hexarelin share the same Trp, D-Phe and C-terminally amidated Lys arrangement.
Weighing 817.97 g/mol, GHRP-2 falls between its two relatives — ipamorelin below it at 711.85 and GHRP-6 above it at 873.01. Each of these is a small molecule, so a milligram supplies far more moles than a milligram of any GHRH analogue would, and that is the reason vials of 5 mg or 10 mg cover so much bench work.
The proposed mechanism
GHS-R1a, the receptor GHRP-2 activates, is a class A GPCR present both on somatotrophs of the anterior pituitary and within hypothalamic tissue. Binding recruits Gq, phospholipase C is switched on, and the two second messengers it generates — inositol trisphosphate and diacylglycerol — push cytosolic calcium upward, which in turn triggers exocytosis of stored granules. Alongside this, the literature reports a lessening of somatostatin inhibition, so the brake eases as the accelerator is pressed. Another notable trait is substantial ligand-free activity, the reason this receptor features so prominently in studies of inverse agonism.
Head-to-head studies keep returning to one feature: this compound does not act on the somatotropic axis alone. Prolactin climbs, and so do corticotropin and cortisol — further than under ipamorelin when both are matched for GH-releasing strength. Calling that a flaw depends entirely on the design in hand. Where the goal is a clean somatotroph readout it is noise; where the question concerns how secretagogue receptors intersect with the adrenal axis it is the measurement. A further reported contrast is weaker action on hunger signalling than GHRP-6 shows, and that is the dimension along which the two first-generation hexapeptides most clearly part company.
Published research
Receptor discovery and characterisation
Before anyone knew what molecule the body used to occupy it, GHS-R1a was pinned down as a receptor quite separate from the GHRH receptor, and GHRP-2 was one of the compounds that made the case. Laboratories still reach for it as a benchmark ligand — in competition binding, in calcium imaging, in assays tracking inositol phosphate build-up, and whenever members of this class are ranked by potency.
Diagnostic endocrinology
Japanese regulators licensed pralmorelin for diagnostic use in gauging how much GH a pituitary can release — an application that calls for exactly what this compound offers, a reproducible response to a standard challenge. The authorisation belongs to a clinical product administered by physicians, and none of it extends to peptide sold for laboratory research.
Comparative secretagogue pharmacology
Rankings within this family almost always include it, typically alongside the other three hexapeptide-era compounds. How sharply it differs from ipamorelin on selectivity is taken up in ipamorelin vs GHRP-2.
Combination designs
Two receptors converge on the somatotroph through separate messenger systems, which is why protocols routinely pair a ghrelin-receptor ligand with one acting at the GHRH receptor; a ready-mixed research preparation exists combining CJC-1295 and GHRP-2. State the molarity of each component in any such work, since roughly a fourfold difference in mass separates them.
Presentations available
Our stock is lyophilized powder in sealed vials of 5 mg (€50) or 10 mg (€80). Dividing 5 mg by 817.97 g/mol gives about 6.11 micromoles per small vial — some four times what the same weight of a GHRH analogue would supply, and precisely why weighing out equal milligrams across the two receptor systems produces a misleading comparison. Find the class under GHRPs and secretagogues.
Reconstitution and storage at the bench
Running the numbers: add 2 mL of preserved diluent to a 5 mg vial and the result is 2.5 mg/mL, or 2,500 mcg/mL, which puts 250 mcg in every 0.1 mL — ten units on a U-100 barrel. Expressed molar that stock is near 3.06 mM, so reaching an assay concentration of 10 nanomolar calls for a dilution on the order of 300,000-fold, best achieved through successive steps instead of one large jump.
Three residues that usually dominate stability discussion are simply absent here, so re-pairing thiols, oxidised thioethers and hydrolysed amide side chains are not on the list of concerns. The genuine weak point is residue 4: an indole ring absorbs light and breaks down under sustained illumination, giving a specific reason — not a generic one — to keep both powder and solution in the dark. Two large aromatic groups also leave the molecule less water-friendly than its modest size suggests, so allow the cake to go fully into solution and confirm the liquid is clear. Freeze lyophilized vials at −20 °C away from light and damp, and hold reconstituted material refrigerated in aliquots; the peptide storage guide fills in the rest.
Purity, the COA and how to read it
Material is taken to 99% or better on a reversed-phase column, identity is verified by mass, and the certificate matches the lot on the vial. Three things are worth checking. One: does the reported mass agree with 817.97 g/mol, the value for the amidated hexapeptide? Roughly a dalton more and you are looking at the free acid. Two: does it match the compound you ordered rather than a relative? Masses of 873.01 and 711.85 for the other two make this quick, and a mislabelled vial cannot hide on the certificate. Three: recognise the method's blind spot — mirror-image residues weigh exactly what their natural counterparts weigh, so no spectrometric measurement can confirm the three D positions, and assurance has to come from synthesis records, sharp chromatographic separation or a chiral assay run for the purpose. What each analytical section can and cannot demonstrate is covered in our COA reading guide.
Regulatory position
The Japanese diagnostic clearance covers a clinical product given by physicians. In the United States there is no marketing authorisation, no place for the compound in food supplements and no general availability through compounding pharmacies. A licence granted elsewhere, for diagnostics, permits nothing else to be done with laboratory peptide.
Related peptides and further reading
As the original member, GHRP-6 remains the comparator of choice where feeding behaviour is measured; ipamorelin is the contemporary selective standard; hexarelin sits at the potent, unselective end. Across the axis, sermorelin, Modified GRF 1-29 and tesamorelin engage the GHRH receptor and signal through cyclic AMP instead of calcium. For the whole picture, see the GH secretagogue landscape explained.
Questions
What is GHRP-2?
Listed variously as pralmorelin or KP-102, GHRP-2 is a six-residue synthetic peptide: D-Ala, D-2-Nal, Ala, Trp, D-Phe and an amidated Lys. Its mass is 817.97 g/mol and its CAS number 158861-67-7. Pharmacologically it is an agonist of GHS-R1a — the receptor that ghrelin occupies in the body.
In what way does it differ from GHRP-6?
Two residues have been swapped. At the second position, GHRP-6's D-tryptophan gives way to D-2-naphthylalanine, whose fused twin-ring side chain is larger and less polar; most of the potency gain traces back to it. At the first position, histidine gives way to D-alanine, so the residue that peptidases trim first is in the unnatural configuration. Positions three to six are untouched.
Does GHRP-2 influence hormones other than growth hormone?
Yes — reports describe concurrent rises in prolactin as well as in the corticotropin and cortisol pair, exceeding what ipamorelin produces when the two are matched for GH release. Whether that is a nuisance or the point depends on the protocol. Studies aiming at somatotroph signalling in isolation must control for it; studies asking how the secretagogue receptor touches the adrenal axis are measuring it deliberately.
Does it have approval anywhere?
One approval exists: Japanese regulators cleared pralmorelin for diagnostic assessment of the pituitary's capacity to secrete GH, and it is administered there as a licensed pharmaceutical by clinicians. Nothing equivalent applies in the United States, where it is neither authorised for marketing, nor permitted in food supplements, nor commonly compounded. Such a clearance abroad confers no permission to use laboratory peptide for anything else.
How does signalling at GHS-R1a proceed?
The receptor belongs to class A and signals largely through Gq. Ligand binding switches on phospholipase C; the resulting second messengers — inositol trisphosphate plus diacylglycerol — drive a rise in cytosolic calcium, and granule exocytosis follows. A parallel route reported in the literature is relief of somatostatin inhibition. The receptor is also unusual in firing appreciably with no ligand bound at all.
How can GHRP-2 be distinguished from GHRP-6 and ipamorelin on a certificate?
The masses do the work. Since the three compounds weigh 817.97, 873.01 and 711.85 g/mol respectively, the spectrometry panel on the certificate reveals a wrongly labelled vial straight away. Should the reading sit about one dalton high, the terminal amide is missing and you have the free acid.
Which storage sensitivities does GHRP-2 have?
None of the residues prone to the classic failure modes — a thiol that can re-pair, a thioether that can oxidise, an amide that can hydrolyse — appears in this chain, so those worries fall away. What remains is the indole ring of residue four, which absorbs light and can be damaged by extended illumination. Store powder and solution away from light, freezing vials at minus 20 degrees Celsius and refrigerating solution split into aliquots.
Why does GHRP-2 matter historically?
It helped show that somatotrophs could be made to secrete despite blockade of the GHRH receptor, evidence that a second, unknown receptor had to be involved. Cloning of GHS-R1a followed in 1996, and in 1999 ghrelin was recognised as the ligand that occupies it naturally. Papers in this area still cite GHRP-2 as a benchmark agonist.