Ipamorelin is a synthetic pentapeptide that belongs to the growth hormone-releasing peptide (GHRP) family. It was developed at Novo Nordisk in the 1990s and described in 1998 as the first selective growth hormone secretagogue. Its short sequence, its action at the ghrelin receptor and its reported selectivity have made it a frequent reference compound in pituitary signalling research. This article covers the structure of ipamorelin, how it fits into the wider GHRP family and what the original studies reported about its selectivity.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.
Ipamorelin is often discussed alongside GHRH analogues. For that wider context, see our pillar guide to CJC-1295 and ipamorelin in research.
At a glance: ipamorelin
- Name: Ipamorelin
- Synonyms: NNC 26-0161
- Sequence: Aib-His-D-2-Nal-D-Phe-Lys-NH2
- Molecular formula: C38H49N9O5
- Molecular weight: 711.9 g/mol
- CAS number: 170851-70-4
- Form: Lyophilised powder
- Purity: >99% (HPLC)
- Storage: 2-8°C, dark, upright, do not freeze. Keep sealed until use.
Where ipamorelin comes from: the GHRP lineage
The GHRP story begins in the late 1970s and early 1980s with the work of Cyril Bowers and colleagues, who found that small synthetic enkephalin-derived peptides could release growth hormone from pituitary cells. This line of research produced GHRP-6, a hexapeptide reported by Bowers and co-workers in 1984, followed by GHRP-1, GHRP-2 and hexarelin.
These peptides were active at a receptor that, at the time, had no known natural ligand. In 1996 Howard and colleagues cloned this receptor and named it the growth hormone secretagogue receptor (GHS-R). Three years later, Kojima and colleagues identified ghrelin, an acylated 28-amino-acid peptide from the stomach, as its endogenous ligand. GHS-R1a is therefore often called the ghrelin receptor.
Ipamorelin was derived from the GHRP-1 structure. The Novo Nordisk team shortened and modified the sequence to arrive at a five-residue peptide amide.
Structure of ipamorelin
The sequence Aib-His-D-2-Nal-D-Phe-Lys-NH2 contains several non-standard residues, each chosen for a structural reason:
- Aib (alpha-aminoisobutyric acid): a non-proteinogenic amino acid with two methyl groups on the alpha carbon. It restricts conformational freedom and is resistant to many peptidases.
- His (L-histidine): a standard residue retained from earlier GHRP designs.
- D-2-Nal (D-2-naphthylalanine): a bulky aromatic D-amino acid also present in GHRP-2. Aromatic residues in this region are associated with receptor binding in the GHRP series.
- D-Phe (D-phenylalanine): a second aromatic D-residue. D-configuration residues reduce susceptibility to enzymatic cleavage.
- Lys-NH2: a C-terminal lysine amide, which removes the negative charge of a free carboxylic acid.
With a molecular weight of 711.9 g/mol, ipamorelin is small compared with GHRH analogues such as CJC-1295 no DAC, which at 29 residues is around 3.4 kDa. Its size and D-amino acid content contribute to greater stability than linear L-peptides of similar length.
The selectivity finding
The paper that introduced ipamorelin was published by Raun and colleagues in the European Journal of Endocrinology in 1998. The authors characterised the compound in vitro using primary rat pituitary cells and in vivo in rat and swine models.
Their key observation concerned selectivity. Earlier GHRPs such as GHRP-6 and GHRP-2 had been reported to raise ACTH and cortisol, as well as prolactin in some studies, in addition to growth hormone. In the 1998 study, ipamorelin released growth hormone with a potency and efficacy comparable to GHRP-6, but did not produce significant rises in ACTH or cortisol across a wide range of tested concentrations, even well above those that produced a maximal growth hormone response. The authors described it as the first GHRP with selectivity for growth hormone release comparable to that of GHRH.
Why selectivity matters to researchers
For an investigator studying the somatotroph axis, a selective tool compound makes it easier to attribute an observed change to GHS-R1a-mediated growth hormone release rather than to concurrent activation of the hypothalamic-pituitary-adrenal axis. That is one reason ipamorelin has been used as a comparator in later GHS-R studies.
Limits of the evidence
The original selectivity data came from animal models and in vitro systems. Selectivity in one species or assay does not automatically transfer to another, and later studies used varied designs. Claims about ipamorelin should be read against the specific model in which they were reported.
Clinical investigation and regulatory status
Ipamorelin was later licensed for clinical development and investigated in the context of postoperative ileus, as ghrelin receptor agonists had been studied for their effects on gastrointestinal motility. A phase 2 study published by Beck and colleagues in 2014 in the International Journal of Colorectal Disease did not report a significant difference from placebo on its primary endpoint, and development did not progress to approval. Ipamorelin is not an authorised medicine, and our material is not a medicine.
Ipamorelin and GHRH analogues
Because GHRPs act at GHS-R1a while GHRH analogues act at the GHRH receptor, the two classes engage distinct intracellular pathways in the same pituitary cell type. Research from the 1990s reported that GHRPs and GHRH acted synergistically on growth hormone release in some models. This pairing is the reason ipamorelin is frequently discussed with modified GRF (1-29) and with stabilised analogues such as tesamorelin.
Handling the lyophilised material
Ipamorelin is supplied as a dry lyophilised powder in a sealed vial. We recommend storage at 2-8°C, in the dark, upright and not frozen, with the vial kept sealed until use. See our guide on how to store lyophilised peptides for general handling of dry peptide material.
View ipamorelin in the catalogue, or the CJC-1295 no DAC and ipamorelin blend.
Frequently asked questions
What class of compound is ipamorelin?
Ipamorelin is a synthetic growth hormone-releasing peptide (GHRP), also described as a growth hormone secretagogue. It is a pentapeptide amide that acts as an agonist at the growth hormone secretagogue receptor type 1a, the receptor later identified as the ghrelin receptor.
Why is ipamorelin described as selective?
In the 1998 study by Raun and colleagues, ipamorelin released growth hormone in rat and swine models without the marked rises in ACTH and cortisol that had been reported for earlier GHRPs such as GHRP-6 and GHRP-2 across the range tested. The authors called it the first selective growth hormone secretagogue.
Is ipamorelin related to ghrelin?
They share a receptor but not a structure. Ghrelin is a 28-residue acylated peptide discovered in 1999, whereas ipamorelin is a much smaller synthetic molecule designed before ghrelin was identified. Both act at GHS-R1a.
Is ipamorelin an approved medicine?
No. Ipamorelin was investigated in clinical studies, including in postoperative gastrointestinal research, but it has not received a marketing authorisation. Compound Cave supplies it only as a laboratory research material.
How is ipamorelin supplied?
Our ipamorelin is a lyophilised powder at >99% HPLC purity, recommended for storage at 2-8°C in the dark, upright and unfrozen. It is also available as a pre-blended vial with CJC-1295 no DAC.
References
- 1. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139:552-561.
- 2. Bowers CY, Momany FA, Reynolds GA, Hong A. On the in vitro and in vivo activity of a new synthetic hexapeptide that acts on the pituitary to specifically release growth hormone. Endocrinology. 1984;114:1537-1545.
- 3. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273:974-977.
- 4. Kojima M, Hosoda H, Date Y, et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999;402:656-660.
- 5. 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. Int J Colorectal Dis. 2014;29:1527-1534.
For laboratory research use only. Not for human or veterinary use. See our research use only policy.