Research library
Ipamorelin Research Overview: Ghrelin Receptor Selectivity, Preclinical Findings and Discontinued Clinical Work
- Compiled by:
- Peptide Pilots Scientific Content Team
- Reviewed by:
- Peptide Pilots Quality & Compliance review
- Last revised:
What made ipamorelin scientifically distinct among growth hormone secretagogues, and what happened to its clinical development?
Ipamorelin is a synthetic pentapeptide agonist of the growth hormone secretagogue receptor 1a (GHS-R1a, the ghrelin receptor). Its defining published characteristic is selectivity: in the original swine and rat studies it released growth hormone without the concurrent increases in ACTH, cortisol or prolactin seen with earlier GHRPs at comparable doses. It advanced into clinical study for postoperative ileus rather than growth-related indications, and that programme did not proceed to approval after phase 2 results, so no approved product exists.
This page is an educational literature summary for laboratory professionals. It is not medical advice, not a description of product performance, and it does not describe or endorse human or veterinary use. Materials referenced are supplied for controlled laboratory research only.
What is Ipamorelin?
Ipamorelin is a five-residue peptide amide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, containing unnatural residues (α-aminoisobutyric acid and D-2-naphthylalanine) that confer protease resistance and receptor affinity.
In laboratory work it is used as a selective GHS-R1a reference agonist in receptor binding and calcium-mobilisation assays, in pituitary cell culture measuring GH release, and in rodent models of GH-axis physiology and gastrointestinal motility.
Ipamorelin names and identifiers
Also referred to as: NNC 26-0161; growth hormone secretagogue; GHRP analogue; Aib-His-D-2-Nal-D-Phe-Lys-NH2
| Sequence | Aib-His-D-2-Nal-D-Phe-Lys-NH2 |
|---|---|
| Molecular formula | C38H49N9O5 |
| Average molecular weight | ≈711.85 g/mol |
| CAS number | 170851-70-4 |
| Development code | NNC 26-0161 |
| Molecular target | Growth hormone secretagogue receptor type 1a (GHSR, UniProt Q92847) |
| Registry records | ClinicalTrials.gov registrations for postoperative ileus (phase 2) |
Ipamorelin research background
Growth hormone-releasing peptides were developed from the 1980s after the discovery that certain enkephalin-derived peptides released GH through a receptor distinct from the GHRH receptor. The orphan receptor was cloned in 1996 and its endogenous ligand, ghrelin, identified in 1999.
Ipamorelin was reported in 1998 by a group at Novo Nordisk as a pentapeptide with GH-releasing potency comparable to GHRP-6 but without the corticotroph and lactotroph activation that complicated interpretation of earlier secretagogues.
Clinical development shifted toward gastrointestinal motility because GHS-R1a activation stimulates gastric emptying. A phase 2 postoperative ileus programme was conducted, and development did not continue after those results.
Proposed Ipamorelin mechanisms and pathways
Evidence is separated by study type. In-vitro and animal findings describe model systems and do not establish equivalent behaviour in humans.
Ipamorelin in-vitro and cell-based evidence
- Binds GHS-R1a and activates Gq/11 signalling, producing phospholipase C activation, IP3 generation and intracellular calcium mobilisation in receptor-expressing cells.
- In primary pituitary cell culture it stimulates GH release; the response is additive or synergistic with GHRH, consistent with distinct receptors converging on somatotrophs.
- Reported not to displace ligands at the ACTH-releasing pathways activated by earlier GHRPs at equivalent GH-releasing concentrations, which is the basis of the selectivity claim.
Ipamorelin animal-model evidence
- Swine studies reported dose-dependent GH release with no significant change in ACTH, cortisol, prolactin, FSH, LH or TSH, distinguishing it from GHRP-6 and GHRP-2.
- Rat studies reported increased body-weight gain and bone-mineral endpoints with chronic administration, consistent with sustained GH-axis stimulation.
- Rodent gastrointestinal models reported accelerated gastric emptying and reversal of postoperative ileus phenotypes, the basis for the clinical indication chosen.
Published Ipamorelin human-study evidence
- Phase 2 studies in postoperative ileus were conducted; the programme was discontinued and full results are only partially represented in the peer-reviewed literature.
- There are no published long-term human studies of GH-axis endpoints with ipamorelin.
- As a growth hormone secretagogue it is prohibited in sport under the World Anti-Doping Agency code, a regulatory rather than scientific classification.
Published Ipamorelin studies
| Study | Model / type | Research question | Main observation | Citation |
|---|---|---|---|---|
| Raun et al., original characterisation | Swine and rat, in vitro pituitary cells | Can a secretagogue release GH without stimulating ACTH and prolactin? | GH release comparable to GHRP-6, with no significant ACTH, cortisol or prolactin elevation at GH-releasing doses. | European Journal of Endocrinology, 1998 |
| Andersen et al., bone and body composition | Rat, chronic administration | Do sustained GH-axis effects appear at tissue level? | Reported increases in body-weight gain and bone-mineral content endpoints. | Growth Hormone & IGF Research, 2001 |
| Beck et al., postoperative ileus | Rodent models and subsequent human phase 2 work | Does GHS-R1a agonism accelerate gastrointestinal transit after surgery? | Accelerated transit in animal models; the clinical programme was not carried through to approval. | PubMed / ClinicalTrials.gov, 2013 |
| GHS-R1a pharmacology reviews | Receptor pharmacology literature | How does GHS-R1a signalling differ from GHRH receptor signalling? | GHS-R1a couples primarily to Gq/11 with high constitutive activity, whereas the GHRH receptor couples to Gs; the two pathways are complementary at the somatotroph. | Science, 1996 |
Limitations of the Ipamorelin evidence
- The selectivity finding derives principally from the original characterisation studies; independent dose-ranging comparisons against modern secretagogues are limited.
- Human evidence is confined to a discontinued phase 2 gastrointestinal programme, and full trial results are not comprehensively published.
- No human data address chronic GH-axis stimulation, so downstream endpoints such as IGF-1 trajectory, glucose handling and tissue effects are uncharacterised in humans.
- GHS-R1a has high constitutive activity and complex heterodimerisation behaviour, which complicates comparison of agonist potency across assay systems.
- Secondary sources routinely present rodent GH and body-composition findings as if they were human outcomes; the published record does not support that.
Ipamorelin laboratory characteristics
Handling and analytical information reported in the literature and in supplier documentation. Values apply to laboratory materials and are not directions for any other use.
| Appearance | White lyophilised powder |
|---|---|
| Solubility | Soluble in water and aqueous buffers; the naphthylalanine residue increases hydrophobicity relative to natural pentapeptides |
| Lyophilised storage | Commonly stored at −20 °C, desiccated and protected from light |
| Reconstituted handling | Refrigerated; single working aliquots preferred to repeated freeze–thaw cycling |
| Analytical testing | RP-HPLC purity and MS identity per lot; unnatural residues make MS/MS sequence confirmation useful |
| Stability considerations | C-terminal amidation and Aib substitution confer good protease resistance; oxidation of histidine is the main monitored route |
Frequently asked Ipamorelin research questions
Which receptor does ipamorelin activate?
The growth hormone secretagogue receptor 1a (GHS-R1a), the receptor whose endogenous ligand is ghrelin.
How does ipamorelin differ from GHRP-6 or GHRP-2?
In the original swine and rat studies it released growth hormone without significant concurrent elevation of ACTH, cortisol or prolactin, which those earlier peptides produced at comparable GH-releasing doses.
How does it differ from sermorelin or CJC-1295?
Those are GHRH-receptor analogues acting through a Gs-coupled receptor. Ipamorelin acts at the Gq-coupled ghrelin receptor, which is why the two classes are often studied in combination in preclinical work.
Was ipamorelin ever approved for clinical use?
No. Its most advanced clinical work was a phase 2 postoperative ileus programme that did not proceed to approval.
Ipamorelin primary references
- Raun K, Hansen BS, Johansen NL, et al. (1998). Ipamorelin, the first selective growth hormone secretagogue. European Journal of Endocrinology. https://doi.org/10.1530/eje.0.1390552
- Andersen NB, Malmlöf K, Johansen PB, et al. (2001). The growth hormone secretagogue ipamorelin counteracts glucocorticoid-induced decrease in bone formation. Growth Hormone & IGF Research. https://doi.org/10.1054/ghir.2001.0239
- Various (2013). Ghrelin receptor agonists in postoperative ileus: preclinical and clinical study records. PubMed / ClinicalTrials.gov. https://pubmed.ncbi.nlm.nih.gov/?term=ipamorelin+postoperative+ileus
- Howard AD, Feighner SD, Cully DF, et al. (1996). A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. https://doi.org/10.1126/science.273.5277.974
Authorship and revision
Compiled from primary literature and public databases. Every factual statement on this page is traceable to a listed reference. Compiled by Peptide Pilots Scientific Content Team; documentation and compliance review by Peptide Pilots Quality & Compliance review. First published ; last revised . Pages are revised when the cited literature changes materially.
Catalogue reference
Peptide Pilots supplies Ipamorelin as a laboratory reagent with per-lot RP-HPLC and mass-spectrometry documentation. Quantities, testing, packaging and fulfilment details are on the catalogue page.
Related catalogue products
Laboratory reagents supplied by Peptide Pilots from the Growth Hormone & Body-Composition Research tier. Research use only; not for human or veterinary use.
