GHRP-2 Research, Specifications & Scientific Information
GHRP-2, whose international non-proprietary name is pralmorelin, is a synthetic hexapeptide agonist at the growth hormone secretagogue receptor. It is approved in Japan as a diagnostic agent for provocative testing of growth hormone secretion, and is not approved in the United States for any use.
Category: GHRH analogues and GH secretagogues
Introduction
GHRP-2 occupies an unusual position in this catalogue: it is the only growth hormone secretagogue that a regulator anywhere has approved for anything. In Japan, pralmorelin hydrochloride is a licensed diagnostic agent — an intravenous provocative test of pituitary growth hormone secretion. That is the whole of its approved status. It is not approved as a therapy in Japan or anywhere else, it is not approved at all in the United States, and the approval covers a manufactured diagnostic product rather than the molecule as a laboratory reagent.
The reason it got that far is a matter of clinical practicality rather than pharmacological novelty. The reference test for adult growth hormone deficiency, the insulin tolerance test, is contraindicated in some patients because of the hypoglycaemia it deliberately induces [8]. A peptide that reliably provokes growth hormone release in under an hour with a reproducible threshold is a useful substitute, and that is the case GHRP-2's clinical literature actually makes.
What Is GHRP-2?
GHRP-2 is a synthetic hexapeptide: D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2. It belongs to the growth hormone-releasing peptide family, the synthetic secretagogues that led to the discovery of the growth hormone secretagogue receptor [3] and, through it, to the identification of ghrelin as that receptor's endogenous ligand [6]. The story of how these compounds were developed, and of how a chemistry programme ended up revealing a hormone nobody had been looking for, is set out in the review literature on the class [7].
Its international non-proprietary name is pralmorelin; its development code was KP-102. It acts directly on pituitary somatotrophs, which is what makes it useful as a test of pituitary reserve rather than of the hypothalamic signal above it [1].
Two things distinguish it within its own family. It is among the most potent members of that family, and unlike ipamorelin it engages the corticotroph axis as well as the somatotroph axis — raising ACTH and cortisol alongside growth hormone [4].
GHRP-2 Specifications
- Compound name
- GHRP-2
- Full chemical name
- D-Alanyl-3-(2-naphthalenyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide
- Aliases
- Pralmorelin, Growth hormone-releasing peptide 2, KP-102, D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH2
- Development code
- KP-102
- CAS number
- 158861-67-7
- PubChem CID
- 6918245
- UNII
- E6S6E1F19M
- Compound type
- Synthetic hexapeptide
- Peptide family
- Growth hormone secretagogues (ghrelin receptor agonists)
- Amino acid sequence
- D-Ala-D-2-Nal-Ala-Trp-D-Phe-Lys-NH₂
- Sequence length
- 6 residues
- Molecular formula
- C45H55N9O6
- Molecular weight
- 817.99 g/mol
- Primary target
- Growth hormone secretagogue receptor 1a (GHS-R1a, the ghrelin receptor)
- Secondary targets
- Not publicly characterised
- Receptor family
- Class A (rhodopsin-like) G protein-coupled receptors
- Agonist / antagonist status
- Agonist at the growth hormone secretagogue receptor
GHRP-2 is written in three-letter notation because three of its six residues cannot be expressed in single-letter code. Position 1 is D-alanine, position 2 is the D-enantiomer of 3-(2-naphthyl)alanine, position 5 is D-phenylalanine, and the C-terminus is an amide; only the alanine at position 3, the tryptophan at position 4 and the lysine at position 6 are ordinary L-amino acids. The FDA/NCATS Global Substance Registration System records the substance as a chemical rather than a protein under UNII E6S6E1F19M, with CAS registry number 158861-67-7, molecular formula C45H55N9O6 and a calculated mass of 817.98; PubChem compound identifier 6918245 resolves to the same substance. The international non-proprietary name is pralmorelin, and the pharmaceutical salt used in the Japanese diagnostic product is the dihydrochloride, which the register carries separately under UNII R4AVR27MM8. The supplier catalog for this reagent carries no CAS number for it; the number published here is the register's. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.
Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.
How Does GHRP-2 Work?
The receptor is the growth hormone secretagogue receptor 1a, cloned from pituitary and hypothalamus in 1996 as the target through which the synthetic secretagogues act [3]. It is a class A, rhodopsin-like G protein-coupled receptor, and its endogenous ligand is ghrelin, an acylated peptide from the stomach [6]. It signals principally through Gq and phospholipase C.
That places GHRP-2 on the opposite side of a clean pharmacological divide from the growth hormone-releasing hormone analogues. Sermorelin, tesamorelin and the CJC-1295 forms act at a class B1 receptor through Gs and cyclic AMP; GHRP-2 acts at a class A receptor through a different second messenger. The practical consequence is visible in the diagnostic literature: administering a GHRP together with GHRH produces a response larger than either alone, because two independent routes into the same cell are being engaged [1].
GHRP-2 Mechanism of Action
In vitro research
The receptor assignment for this class was made pharmacologically before it was made molecularly. Profiling secretagogues against GHRP antagonists and growth hormone-releasing hormone antagonists separated the two families by their blockade patterns, and GHRP-2 falls on the GHRP side [4]. The receptor itself was subsequently cloned from pituitary and hypothalamic tissue and shown to mediate the action of the synthetic secretagogues directly [3].
In primary rat pituitary cells, the comparative study that introduced ipamorelin measured growth hormone release across the family; GHRP-6 released growth hormone with an EC50 of 2.2 ± 0.3 nmol/l at an Emax defined as 100 per cent, and ipamorelin at 1.3 ± 0.4 nmol/l and 85 ± 5 per cent [4]. The distinguishing GHRP-2 result in that study came from whole animals rather than cells and is described in the preclinical section below.
What Is GHRP-2 Being Researched For?
Published research on GHRP-2 is dominated by one application, with several smaller lines around it:
- Provocative testing for adult growth hormone deficiency — the validation study behind the Japanese diagnostic approval, and subsequent comparisons against the insulin tolerance test [8, 11].
- Provocative testing in children — intravenous and intranasal diagnostic studies, and a later evaluation against the insulin tolerance test [1, 10].
- Hypothalamic-pituitary-adrenal axis testing — the ACTH response as a diagnostic signal [9].
- Growth hormone pulsatility under continuous stimulation — a 24-hour infusion study in women [5].
- Comparative secretagogue pharmacology — where GHRP-2 serves as a reference compound [4, 7].
The clinical work above studied pharmaceutical-grade material in people under clinical supervision, usually within diagnostic protocols. None of it is research into, or evidence about, research-grade material supplied for laboratory use.
Human Research on GHRP-2
Human clinical research
Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.
Validation of the provocative test in adult growth hormone deficiency
Population. 77 healthy participants and 58 patients with a peak growth hormone below 3 µg/l on the insulin tolerance test [8].
Endpoint and duration. After an overnight fast, a single 100 µg intravenous administration, with blood sampled over the following two hours and growth hormone measured by immunoradiometric assay [8].
Result. The serum growth hormone peak occurred within 60 minutes in every participant. Peak concentrations were significantly lower in patients (1.36 ± 2.60 µg/l) than in the healthy group (84.6 ± 60.9 µg/l), p < 0.001, with no difference between hypothalamic and pituitary disease. Responses were unaffected by sex, slightly lower in older participants and those with adiposity, and reproducible on repeat testing. The concentration at which sensitivity crossed specificity fell between 15 and 20 µg/l, and a cut-off of 15 µg/l corresponded to the insulin tolerance test's 3 µg/l [8].
Limitations. A validation study of a diagnostic threshold, not a study of any clinical outcome. It establishes that the test discriminates, in the population enrolled, against a reference test that itself has limitations.
Comparison against the insulin tolerance test
Population. Japanese patients evaluated for adult growth hormone deficiency [11].
Endpoint and duration. A comparison of the arginine test and the GHRP-2 test against the insulin tolerance test as the reference standard [11].
Result. The study addressed which alternative test best reproduces the reference classification when the insulin tolerance test is contraindicated. Its contribution is diagnostic agreement, not any measure of effect on a person.
Limitations. A single-country comparison against a reference standard whose own thresholds are debated.
Diagnostic studies in children
Population. 24 children undergoing evaluation for growth hormone deficiency, each of whom received at least one conventional provocative agent in addition to intravenous GHRH and GHRP-2 [1]. Separately, 56 children with growth disorders [10].
Endpoint and duration. In the first study, growth hormone responses to intravenous GHRP-2 were compared with responses to conventional agents and to GHRH, with a subset receiving both releasing factors together and a further subset receiving intranasal administration at 5 to 20 µg/kg. In the second, a 2 µg/kg intravenous administration was compared against the insulin tolerance test [1, 10].
Result. In the first study the responses to GHRH and to GHRP-2 were similar in each child and both predicted pituitary reserve more reliably than the conventional agents; the combined administration produced a synergistic response in the 12 children who received it, and all 15 children given the intranasal form responded significantly [1]. In the second, peak concentrations correlated favourably with the insulin tolerance test (p < 0.0001) and were significantly lower in children with growth hormone deficiency (median 3.39 µg/l) than without (25.10 µg/l); the sensitivity-specificity crossing point was again 15 µg/l, and the test took an hour or less [10].
Limitations. Small single-centre diagnostic studies, and in the first a design in which the same children received several agents in sequence.
ACTH response and adrenal axis testing
Population. Patients with hypopituitarism [9].
Endpoint and duration. Comparison of the ACTH response to GHRP-2 with the ACTH response to the insulin tolerance test [9].
Result. Patients with a significant ACTH response to the insulin tolerance test also responded to GHRP-2, and those without a response to one also lacked a response to the other. The authors concluded the test may be useful for diagnosing secondary adrenal insufficiency [9].
Limitations. A concordance study in a small clinical population, offered by its authors as a suggestion rather than a validated replacement.
Preclinical Research on GHRP-2
Animal research
The animal result that matters most for GHRP-2 is a negative one about a different compound. In conscious swine, a comparison across the secretagogue family found that none of the compounds tested altered plasma FSH, LH, prolactin or TSH — but GHRP-2 and GHRP-6 both raised plasma ACTH and cortisol, while ipamorelin did not, even at amounts more than 200-fold above its ED50 for growth hormone release [4].
That finding is usually quoted to establish ipamorelin's selectivity. Read the other way, it is the clearest published characterisation of GHRP-2's own hormonal profile: it engages the corticotroph axis as well as the somatotroph axis. The clinical literature has since treated that property as useful rather than as a liability, using the ACTH response diagnostically [9].
In the same comparison, GHRP-2 in swine showed an ED50 of 0.6 nmol/kg with an Emax of 56 ± 6 ng growth hormone per ml plasma — more potent than GHRP-6 at 3.9 ± 1.4 nmol/kg but with a lower maximal response than GHRP-6's 74 ± 7 ng/ml [4].
Findings described in this section were observed in animals, and nothing in them establishes anything about humans.
Other Areas of GHRP-2 Research
Human clinical research
Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.
Beyond diagnosis, the most mechanistically interesting human work asked what continuous rather than pulsed stimulation does to an axis that is normally pulsatile. A study in women administered a growth hormone-releasing peptide by continuous 24-hour infusion and analysed the resulting secretion by pulsatile, entropic and nyctohemeral measures — that is, by pulse structure, by the regularity of the secretory process, and by its day-night pattern [5]. The question is the same one the long-acting GHRH analogues raise, approached from the other receptor.
A second line is comparative. An early randomised study in children with growth hormone insufficiency and idiopathic short stature set the growth hormone-releasing effects of GHRP-2 directly against those of GHRH(1-29)NH2 — the peptide sold as sermorelin — in the same participants [2]. Comparisons of that kind are rare and are the only sound basis for statements about one family relative to the other.
All of this work was conducted in people, under protocol, with pharmaceutical-grade material.
Current Research Status
- Regulatory status (United States)
- Not approved in the United States. GHRP-2 has not been approved by the U.S. Food and Drug Administration for any indication, diagnostic or therapeutic.
- Investigational status
- Approved in Japan as a diagnostic agent. Pralmorelin hydrochloride is marketed there as an intravenous provocative test of growth hormone secretion in suspected adult growth hormone deficiency, following the validation study conducted by the KP-102 Study Group. That approval is a Japanese regulatory record, attaches to a specific manufactured diagnostic product and a single diagnostic use, and does not extend to the United States, to any therapeutic indication, or to research-grade material. No therapeutic approval exists in any jurisdiction.
- Highest research phase reached
- Approved diagnostic product in Japan; investigator-initiated clinical validation studies continuing
- Approved uses
- Japan only: intravenous provocative testing of growth hormone secretion, as a specific approved diagnostic product. No approved use in the United States.
- Approval is compound-specific
- Yes
Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.
Chemical & Molecular Characteristics
GHRP-2 is a hexapeptide whose composition is half non-standard, which is both why it resists proteolysis and why it cannot be written in single-letter code.
The residues. Position 1 is D-alanine, position 2 the D-enantiomer of 3-(2-naphthyl)alanine, position 3 L-alanine, position 4 L-tryptophan, position 5 D-phenylalanine and position 6 L-lysine, with a C-terminal amide. Three D-residues and a C-terminal amide are the standard devices for making a short peptide survive in plasma.
The register treats it as a small molecule. Unlike the growth hormone-releasing hormone analogues, which the Global Substance Registration System records as proteins with sequences and modifications, GHRP-2 is recorded as a chemical substance under UNII E6S6E1F19M with a structure, a formula of C45H55N9O6 and a calculated mass of 817.98. CAS registry number 158861-67-7 and PubChem compound identifier 6918245 resolve to the same substance.
The salt is a separate substance. The Japanese diagnostic product uses pralmorelin dihydrochloride, which the register carries separately under its own identifier. That distinction matters for any comparison of mass or purity figures between a pharmaceutical product and a reagent.
The catalog carries no registry number. The supplier catalog entry for this reagent has an empty CAS field; the number published here is the register's, not the catalog's.
Analytical Specifications
- Physical form
- Lyophilized powder
- Appearance
- White to off-white lyophilized solid
- Lot number
- RP-2609-073
- Tested purity
- ≥99% by HPLC
- Storage
- −20 °C, protect from light, desiccate
Analytical figures are lot-specific. Fields the catalog does not carry for the current lot are omitted rather than filled with a typical value. The certificate of analysis and the safety data sheet for the exact lot supplied are provided with a laboratory order; no purity figure on this page is a substitute for that document.
Frequently Asked Questions
What is GHRP-2?
What is pralmorelin?
How does GHRP-2 work?
Is GHRP-2 FDA approved?
What is the GHRP-2 stimulation test?
Does GHRP-2 affect cortisol?
How does GHRP-2 differ from GHRP-6?
Has GHRP-2 been studied in children?
Scientific References
- Diagnostic studies with intravenous and intranasal growth hormone-releasing peptide-2 in children of short stature The Journal of clinical endocrinology and metabolism; 1995. PMID 7559885 doi:10.1210/jcem.80.10.7559885
- Growth hormone (GH)-releasing effects of synthetic peptide GH-releasing peptide-2 and GH-releasing hormone (1-29NH2) in children with GH insufficiency and idiopathic short stature Metabolism: clinical and experimental; 1995. PMID 7666796 doi:10.1016/0026-0495(95)90016-0
- A receptor in pituitary and hypothalamus that functions in growth hormone release Science (New York, N.Y.); 1996. PMID 8688086 doi:10.1126/science.273.5277.974
- Ipamorelin, the first selective growth hormone secretagogue European journal of endocrinology; 1998. PMID 9849822 doi:10.1530/eje.0.1390552
- Tripartite neuroendocrine activation of the human growth hormone (GH) axis in women by continuous 24-hour GH-releasing peptide infusion: pulsatile, entropic, and nyctohemeral mechanisms The Journal of clinical endocrinology and metabolism; 1999. PMID 10372723 doi:10.1210/jcem.84.6.5687
- Ghrelin is a growth-hormone-releasing acylated peptide from stomach Nature; 1999. PMID 10604470 doi:10.1038/45230
- Development of growth hormone secretagogues Endocrine reviews; 2005. PMID 15814848 doi:10.1210/er.2004-0019
- A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency European journal of endocrinology; 2007. PMID 17609397 doi:10.1530/EJE-07-0066
- Diagnostic usefulness of the growth hormone-releasing peptide-2 test as a substitute for the insulin tolerance test in hypopituitarism Endocrine journal; 2008. PMID 18493103 doi:10.1507/endocrj.k07e-168
- Growth hormone response to GH-releasing peptide-2 in children Journal of pediatric endocrinology & metabolism : JPEM; 2010. PMID 20662346 doi:10.1515/jpem.2010.078
- The arginine and GHRP-2 tests as alternatives to the insulin tolerance test for the diagnosis of adult GH deficiency in Japanese patients: a comparison Endocrine journal; 2013. PMID 23079545 doi:10.1507/endocrj.ej12-0230
Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.
Research-Use Information
For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.
Related laboratory reagent: GHRP-2 specifications and lot documentation