Ipamorelin

What Ipamorelin is

Ipamorelin is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, developed at Novo Nordisk in Denmark in the mid-1990s as part of a programme to find small growth hormone secretagogues with a cleaner pharmacological profile than the growth-hormone-releasing peptides (GHRPs) that preceded it [1]. The discovery paper by Raun and colleagues, published in the European Journal of Endocrinology in 1998, describes it as "the first selective growth hormone secretagogue", the word "selective" referring to its ability to release growth hormone (GH) without the accompanying release of adrenocorticotrophic hormone (ACTH) and cortisol that the earlier GHRPs produced [1]. The compound was later licensed to the Swiss company Helsinn, which took it into phase 2 clinical trials for postoperative ileus; that programme is discussed below. Ipamorelin has never been licensed as a medicine in any jurisdiction.

Structurally the molecule is unusual among the peptides in this catalogue. Three of its five residues are non-natural: α-aminoisobutyric acid (Aib) at the N-terminus, D-2-naphthylalanine (D-2-Nal) at position 3 and D-phenylalanine at position 4. Only histidine and lysine are proteinogenic L-amino acids, and the C-terminus is an amide rather than a free acid. The D-residues and the Aib resist proteolysis, the naphthyl and phenyl side chains supply the hydrophobic contacts the ghrelin receptor requires, and the N-terminal amine, histidine imidazole and lysine ε-amine give the peptide a net positive charge at neutral pH [1]. The sequence belongs to the same family as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) and GHRP-2.

Research-grade Ipamorelin is supplied as a white to off-white lyophilised powder, normally as the acetate salt produced by solid-phase synthesis followed by preparative reversed-phase HPLC. The reference identifiers for the free base are in the table; the values on any batch certificate should agree with them within the precision of the method used.

How the literature describes its mechanism

Unlike many compounds in the research-peptide market, Ipamorelin has a defined molecular target. It is an agonist at the growth hormone secretagogue receptor type 1a (GHS-R1a), a G-protein-coupled receptor cloned by Howard and colleagues at Merck in 1996 from pituitary and hypothalamic cDNA using the non-peptide secretagogue MK-0677 as the probe ligand [2]. The receptor was for three years an orphan, in the sense that the synthetic peptides and small molecules that activated it were known but the endogenous ligand was not. That ligand was identified in 1999 by Kojima and colleagues as ghrelin, a 28-residue acylated peptide secreted mainly by the stomach, whose n-octanoyl modification at serine 3 is required for receptor activation [3]. The GHRPs, Ipamorelin among them, are therefore best described as ghrelin mimetics: they were designed before the hormone was known, by screening for GH release, and turned out to act at ghrelin's receptor.

GHS-R1a couples principally through Gαq/11 to phospholipase C and a rise in intracellular calcium, and shows marked constitutive activity in heterologous expression systems. In the somatotroph the calcium signal triggers exocytosis of GH-containing granules; the receptor is also expressed in the arcuate nucleus, where agonists increase growth-hormone-releasing hormone (GHRH) release. The GHRH receptor is a separate Gαs-coupled receptor, which is why GHRPs and GHRH act synergistically on GH release [1, 2].

Raun and colleagues characterised Ipamorelin in several of these systems. In primary rat pituitary cell cultures it released GH with a potency (EC50 of the order of 1 nM) and efficacy comparable to GHRP-6, and the response was blocked by a GHRP-receptor antagonist but not by a GHRH-receptor antagonist, which established that it acts through the GHRP (ghrelin) receptor rather than the GHRH receptor [1]. The property that the authors emphasised, and that gave the paper its title, was what the compound did not do. In anaesthetised swine, GHRP-2 and GHRP-6 released ACTH and cortisol alongside GH, whereas Ipamorelin did not raise ACTH or cortisol even at doses many times those required for maximal GH release; nor did it affect prolactin, thyrotrophin, follicle-stimulating hormone or luteinising hormone [1]. On this basis the compound was described as having a GH-release profile closer to that of GHRH itself than to that of the other GHRPs. The basis of the selectivity was not explained in the original paper and has not been fully resolved since.

A second strand of mechanism concerns the gut. GHS-R1a is expressed on enteric cholinergic neurones, and ghrelin and its mimetics stimulate gastric motility. In a rat organ-bath preparation Greenwood-Van Meerveld and colleagues showed that Ipamorelin at 1 µM restored the contractile response of gastric fundus strips after it had been suppressed by surgical manipulation, and proposed that the prokinetic effect runs through ghrelin receptors on excitatory cholinergic motor neurones [9]. This is the mechanism Helsinn's clinical programme was intended to exploit.

For an in-vitro programme the published readouts are GH release from primary pituitary cells, calcium mobilisation or inositol phosphate accumulation in cells expressing recombinant GHS-R1a, radioligand displacement at the same receptor, and contractility of isolated gastrointestinal smooth muscle. The compound is active at low nanomolar concentrations in receptor-expressing systems, and the receptor's constitutive activity means that assay baselines need to be characterised before small agonist effects are interpreted.

The research record

Ipamorelin is better characterised than most compounds sold for research, because it passed through a pharmaceutical development programme with formal toxicology, pharmacokinetics and controlled clinical trials. It is nonetheless a compound whose development stopped, and the record should be read with that in mind.

Discovery and early pharmacology. The Raun paper remains the primary reference for the compound's pharmacology in rats and pigs, and its selectivity findings have not been contradicted by later work [1]. The Novo Nordisk group went on to use Ipamorelin as a lead for further secretagogue series, and the internal designation NNC 26-0161 appears in some of that literature.

Bone and growth studies in rats. Three papers from Danish and Swedish groups examined what the compound does to the skeleton of the growing or adult rat. Johansen and colleagues reported in 1999 that two weeks of treatment increased body weight and longitudinal bone growth (measured at the tibial growth plate by tetracycline labelling) in young female rats, with a magnitude comparable to that of GH itself and accompanied by a rise in circulating IGF-I [4]. Svensson and colleagues at Gothenburg treated adult female rats for twelve weeks with Ipamorelin, GHRP-6, GH or vehicle, and found that both secretagogues increased body weight and total tibial and vertebral bone mineral content; the increase disappeared when adjusted for body weight, and volumetric bone density was unchanged, which the authors interpreted as larger bones rather than denser ones [5]. Andersen and colleagues at Aarhus showed in 2001 that in adult rats given prednisolone, a glucocorticoid that suppresses bone formation, Ipamorelin counteracted the fall in bone formation rate [6]. These are small-animal studies with GH-dependent endpoints; they establish nothing about bone in any other species.

Pharmacokinetics in humans. The only published human pharmacokinetic study is from Gobburu, Agersø, Jusko and Ynddal, in Pharmaceutical Research in 1999, using data from Novo Nordisk's phase 1 work [7]. Healthy male volunteers, eight per dose level, received 15-minute intravenous infusions at five rates between about 4 and 140 nmol/kg, and plasma Ipamorelin and serum GH were modelled together. The authors fitted a two-compartment pharmacokinetic model with an elimination half-life of the order of two hours, and an indirect-response pharmacodynamic model in which the compound stimulates GH release from a pool that is depleted and resynthesised, which accounted for the pulsatile, tolerance-prone GH response. The postoperative ileus programme. Helsinn Healthcare licensed Ipamorelin from Novo Nordisk and developed it, as an intravenous ghrelin mimetic, for the delayed return of bowel function that follows abdominal surgery. The preclinical rationale was set out in two papers from Beverley Greenwood-Van Meerveld's laboratory in Oklahoma. In the first, in the Journal of Pharmacology and Experimental Therapeutics in 2009, Ipamorelin given intravenously after intestinal manipulation in rats accelerated gastrointestinal transit and the recovery of faecal output in a dose-related way [8]. In the second, in the Journal of Experimental Pharmacology in 2012 (with Claudio Pietra of Helsinn as a co-author), the same surgical model produced marked delay of gastric emptying, with about 78% of a radiolabelled meal remaining in the stomach at 15 minutes in vehicle-treated animals; Ipamorelin at 0.014 µmol/kg intravenously reduced this to about 52%, close to the 44% seen in unoperated controls, and restored gastric smooth-muscle contractility in the organ bath [9].

The clinical result was published by Beck, Sweeney and McCarter on behalf of the Ipamorelin 201 Study Group in the International Journal of Colorectal Disease in 2014 [10]. This was a phase 2, randomised, double-blind, placebo-controlled proof-of-concept study (NCT00672074) in patients undergoing bowel resection, who received intravenous Ipamorelin or placebo twice daily for up to seven days. The primary endpoint was time to first tolerated meal. The median was 25.3 hours with Ipamorelin against 32.6 hours with placebo, a difference that did not reach statistical significance (p = 0.15), and none of the secondary efficacy analyses showed a significant difference either. Treatment-emergent adverse events were reported in 87.5% of the Ipamorelin group and 94.8% of the placebo group, and the authors described the compound as well tolerated. A second phase 2 study was conducted but has not been reported in a peer-reviewed journal. Helsinn did not take the compound into phase 3, and no marketing application was filed anywhere. The programme is, in short, a controlled trial that produced a negative result on its primary endpoint, and it is the reason Ipamorelin exists today only as a research chemical.

Later commentary. Sigalos and Pastuszak's 2018 review of growth hormone secretagogues surveys the class, including Ipamorelin, and notes that the human evidence for most of these compounds is thin and that the long-term consequences of raising GH and IGF-I by this route have not been studied [11]. There are no published controlled trials of Ipamorelin for any indication other than postoperative ileus.

Taking the record as a whole. Ipamorelin is a potent, selective GHS-R1a agonist with a clean endocrine profile in pigs, GH-dependent effects on growth and bone in rats, a short half-life in humans, a formal phase 2 programme that failed its primary endpoint, and no licence anywhere. That is a sound basis for in-vitro work on the ghrelin receptor and on GH secretion. It is not a basis for therapeutic claims of any kind, and this page makes none.

Regulatory status in the United Kingdom

Ipamorelin is not licensed as a medicine in the UK or anywhere else. It has no marketing authorisation, no monograph in the British, European or United States pharmacopoeias, and no approved therapeutic use; the related compound pralmorelin (GHRP-2) is approved in Japan as a diagnostic agent, but Ipamorelin is not. BuyUK Peptides supplies it as a research chemical for in-vitro laboratory use under the Terms of Sale. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for ensuring their use of the material complies with the laws and institutional rules that apply to them. The Medicines and Healthcare products Regulatory Agency (MHRA) treats peptides of this kind, when presented or supplied for administration to people, as unlicensed medicinal products; supply for research use sits outside that regime only so long as the material is genuinely supplied and used for research. Our guide to the UK rules on research compounds sets this out in more detail.

The World Anti-Doping Agency's Prohibited List names Ipamorelin explicitly. It appears in section S2.2.4, "growth hormone releasing factors", under "growth hormone secretagogues (GHS) and their mimetics", alongside anamorelin, capromorelin, ibutamoren, lenomorelin (ghrelin), macimorelin and tabimorelin, with the GH-releasing peptides GHRP-2 (pralmorelin), GHRP-6 and hexarelin in the same sub-section [12]. Section S2 is prohibited at all times, in and out of competition; the 2026 list, in effect from 1 January 2026, carries the wording quoted here. Any researcher whose institution is subject to anti-doping rules should be aware of this.

Handling, storage and stability

Ipamorelin is supplied lyophilised in a glass vial with a rubber stopper and an aluminium flip-off crimp. It is a small, basic, unlipidated peptide with no cysteine, methionine or tryptophan and three protease-resistant non-natural residues, and is in consequence one of the more robust compounds in the catalogue.

Sealed vial. Store at 2–8 °C for routine use and at −20 °C or below for storage beyond a few months. Protect from light. Avoid repeated freeze–thaw cycles. Allow a refrigerated vial to reach room temperature before opening, so that moisture does not condense onto the cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile bacteriostatic water, sterile water, or a buffer appropriate to the assay. A pentapeptide carrying a net positive charge dissolves readily in water and in phosphate-buffered saline at several milligrams per millilitre; supplier datasheets also report solubility in DMSO and ethanol at 20–30 mg/ml where a concentrated organic stock is wanted. Add the solvent down the side of the vial and swirl gently; the cake should clear within seconds. The reconstitution calculator gives the volume to add for a target concentration.

Reconstituted solution. Keep at 2–8 °C and protect from light. The chemical stability of Ipamorelin in clean aqueous solution is good, because the residues most prone to deamidation and oxidation are absent, and the C-terminal amide is stable in neutral buffers. The conservative practice for a research solution is to use it within 28 days and to discard it if it becomes cloudy. Aliquoting into single-use volumes and freezing at −20 °C is a sensible alternative where the buffer permits it.

Adsorption. The two aromatic D-residues give the molecule a hydrophobic face, and at low concentrations basic hydrophobic peptides of this kind can adsorb to untreated glass and polystyrene. For dilute working solutions, low-binding polypropylene or a carrier protein in the diluent is advisable, and a 0.22 µm PVDF or PES membrane is preferable to nylon where filtration is required.

What a sound certificate for Ipamorelin looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For Ipamorelin a certificate should contain the following, and a reader should be able to check each item against this monograph.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection at 214 or 220 nm reports purity as the area of the main peak as a percentage of all integrated peaks; the naphthyl group also absorbs at 280 nm, which gives a second, more selective wavelength. A good batch of Ipamorelin shows a single dominant peak with purity of 98% or above; 99% and above is routine for a peptide of five residues. The impurities to expect are deletion sequences, the des-Aib tetrapeptide in particular, and the diastereomer formed by racemisation of the histidine during coupling, which elutes close to the main peak and is the impurity most worth asking about if a chromatogram shows a shoulder.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. For Ipamorelin the average molecular weight is 711.85 Da and the monoisotopic mass is approximately 711.39 Da. A peptide of this size and basicity usually appears as the singly charged [M+H]+ ion at about 712.4 and the doubly charged [M+2H]2+ ion at about 356.7, and a certificate may report either or a deconvoluted mass. The observed mass should agree with the theoretical value to within about 0.3 Da. A mass one unit higher than expected would indicate hydrolysis of the C-terminal amide to the free acid, and a mass 85 Da lower would indicate loss of the Aib residue.

Net peptide content. Lyophilised peptides contain bound water and counter-ions, so the mass of powder in the vial is more than the mass of peptide. For a basic peptide with three ionisable amines the counter-ion fraction is larger than for a neutral or acidic one, and a trifluoroacetate salt carries more than an acetate. Net peptide content, where reported, expresses the fraction that is actual peptide, and it matters for preparing solutions of accurate concentration. The certificate should also state which counter-ion is present; residual trifluoroacetate can itself affect cell assays and is a reason to prefer acetate-exchanged material.

Endotoxin. Where the batch has been tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram. This is relevant to the primary pituitary cell and enteric-neurone preparations in which Ipamorelin is most often studied, where endotoxin can itself alter secretory and contractile responses.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

Ipamorelin belongs to the growth hormone secretagogue family and is most often discussed alongside the GHRH analogues, which act at a different receptor on the same somatotroph. CJC-1295 without DAC, a modified 29-residue fragment of GHRH, is the GHRH-receptor agonist in the catalogue, and the two are studied together in pituitary cell systems because the GHRH and ghrelin receptors signal through different G-proteins and give an additive or synergistic GH response in vitro [1, 2]. Within the ghrelin-receptor family, GHRP-6 and GHRP-2 (pralmorelin) are the historical comparators against which Ipamorelin's selectivity was defined [1], and all three appear beside it in the WADA list [12]. Ghrelin itself is the appropriate reference agonist for any receptor-level assay [3].

Frequently asked questions

Is Ipamorelin a natural hormone? No. It is an entirely synthetic pentapeptide designed in the 1990s [1]. It mimics the action of ghrelin, a natural hormone identified a year after Ipamorelin was published, at the GHS-R1a receptor [3].

What does "selective" mean in its name? In the discovery paper the term refers to release of growth hormone without the ACTH and cortisol release that GHRP-6 and GHRP-2 produce in the same animal model [1]. It does not mean the compound acts on only one tissue; the ghrelin receptor is expressed in the pituitary, hypothalamus and gut.

Has it ever been approved as a medicine? No, in any country. It reached phase 2 in a programme for postoperative ileus, did not meet its primary endpoint, and was not developed further [10].

Are there any human trials? One published phase 1 pharmacokinetic study in healthy volunteers [7] and one published phase 2 trial in bowel-resection patients [10]. There are no published trials for any other purpose.

Is it on the WADA list? Yes, by name, in section S2.2.4 under growth hormone secretagogues and their mimetics; the prohibition applies at all times [12].

Can you advise on how it is used? No. The material is supplied for in-vitro research only, and we do not provide guidance on its use in people or animals.

How long does a sealed vial last? Short lyophilised peptides of this kind, with protease-resistant non-natural residues and no oxidation-prone side chains, are stable for years at −20 °C and for many months at 2–8 °C. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. 1998;139(5):552–561. doi:10.1530/eje.0.1390552. PMID 9849822.
2. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974–977. doi:10.1126/science.273.5277.974.
3. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402(6762):656–660. doi:10.1038/45230.
4. Johansen PB, Nowak J, Skjærbæk C, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Hormone & IGF Research. 1999;9(2):106–113. doi:10.1054/ghir.1999.9998. PMID 10373343.
5. Svensson J, Lall S, Dickson SL, et al. The GH secretagogues ipamorelin and GH-releasing peptide-6 increase bone mineral content in adult female rats. Journal of Endocrinology. 2000;165(3):569–577. doi:10.1677/joe.0.1650569. PMID 10828840.
6. Andersen NB, Malmlöf K, Johansen PB, Andreassen TT, Ørtoft G, Oxlund H. The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation of adult rats. Growth Hormone & IGF Research. 2001;11(5):266–272. doi:10.1054/ghir.2001.0239. PMID 11735244.
7. Gobburu JVS, Agersø H, Jusko WJ, Ynddal L. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharmaceutical Research. 1999;16(9):1412–1416. doi:10.1023/A:1018955126402. PMID 10496658.
8. Venkova K, Mann W, Nelson R, Greenwood-Van Meerveld B. Efficacy of ipamorelin, a novel ghrelin mimetic, in a rodent model of postoperative ileus. Journal of Pharmacology and Experimental Therapeutics. 2009;329(3):1110–1116. doi:10.1124/jpet.108.149211.
9. Greenwood-Van Meerveld B, Tyler K, Mohammadi E, Pietra C. Efficacy of ipamorelin, a ghrelin mimetic, on gastric dysmotility in a rodent model of postoperative ileus. Journal of Experimental Pharmacology. 2012;4:149–155. doi:10.2147/JEP.S35396. PMID 27186127.
10. Beck DE, Sweeney WB, McCarter MD; Ipamorelin 201 Study Group. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients. International Journal of Colorectal Disease. 2014;29(12):1527–1534. doi:10.1007/s00384-014-2030-8.
11. Sigalos JT, Pastuszak AW. The safety and efficacy of growth hormone secretagogues. Sexual Medicine Reviews. 2018;6(1):45–53. doi:10.1016/j.sxmr.2017.02.004.
12. World Anti-Doping Agency. The Prohibited List 2026. Section S2.2.4, growth hormone releasing factors. In effect from 1 January 2026. wada-ama.org/en/prohibited-list.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.