Ipamorelin is a five-residue synthetic peptide that activates the growth hormone secretagogue receptor (GHS-R1a), the same receptor later found to respond to the stomach hormone ghrelin. Scientists at Novo Nordisk developed it in the 1990s, and the 1998 paper that introduced it called it the first selective growth hormone secretagogue, because in animal work it released GH without the broad hormonal spillover seen with earlier peptides of its type.
That selectivity is the main reason it still appears in endocrine and receptor pharmacology studies. What follows covers where Ipamorelin came from, how its unusual residues shape its behavior, what the ghrelin receptor does, which model systems have been used, and where the published record is thin.
At a glance
- Class: Synthetic pentapeptide; ghrelin receptor (GHS-R1a) agonist
- Origin: Novo Nordisk, development code NNC 26-0161; first characterized by Raun and colleagues in 1998
- Structure: Aib-His-D-2-Nal-D-Phe-Lys-NH2; C38H49N9O5; 711.9 g/mol; CAS 170851-70-4
- Main research areas: GHS-R1a selectivity, GH axis readouts in rodents, pharmacokinetic-pharmacodynamic modeling, ghrelin receptor ligand design
- Regulatory status: Not FDA approved; WADA S2
Structure and origin
By the early 1990s, several synthetic growth hormone-releasing peptides (GHRPs) were available, including GHRP-1, GHRP-2 and GHRP-6. They were potent, but in animal studies they also raised adrenocorticotropic hormone (ACTH), cortisol and sometimes prolactin. The Novo Nordisk team started from the GHRP-1 structure and shortened and modified it, aiming for a compound that kept GH release and dropped the other endocrine responses (Raun et al., 1998).
The result is only five residues long, and three of them are not standard L-amino acids:
- Aib (α-aminoisobutyric acid) at position 1: a methylated, achiral residue that restricts backbone movement and resists aminopeptidases.
- D-2-naphthylalanine at position 3: a bulky aromatic side chain in the D configuration, a feature shared with GHRP-2.
- D-Phe at position 4: another D-residue that protects against proteolysis and is common to most GHRPs.
The C-terminal lysine is amidated. With a molecular weight just over 700 g/mol, Ipamorelin is one of the smallest peptide ligands for GHS-R1a, which helps explain its use as a reference structure in medicinal chemistry reviews of the receptor (Moulin et al., 2007).
Mechanism: what the research shows
GHS-R1a was cloned in 1996 by a Merck group that used a synthetic secretagogue to fish out the receptor from pituitary and hypothalamic tissue (Howard et al., 1996). It is a G protein-coupled receptor that signals mainly through Gq, phospholipase C and a rise in intracellular calcium. That pathway is separate from the GHRH receptor, which works through Gs and cAMP, so secretagogues and GHRH analogs are often studied as two independent inputs to the somatotroph.
In the original characterization, Ipamorelin released GH from primary rat pituitary cells with potency in the same range as GHRP-6, and in anesthetized rats and conscious swine it produced GH responses comparable to other secretagogues (Raun et al., 1998). The difference was in what else moved. Across a wide range of exposure levels in swine, the authors reported that ACTH and cortisol stayed close to baseline with Ipamorelin, while GHRP-6 and GHRP-2 raised them. That profile is what “selective” refers to: selective for GH release among pituitary outputs, not selective for one receptor over another.
Key areas of study
Endocrine selectivity
The swine and rat comparisons in the 1998 paper remain the central dataset. They set Ipamorelin against GHRP-6, GHRP-2 and non-peptide secretagogues in the same models, measuring GH, ACTH, cortisol, prolactin, LH and FSH (Raun et al., 1998). Later reviews of the secretagogue class cite this work when discussing how structural changes separate GH release from adrenal axis effects (Isidro and Cordido, 2006).
Longitudinal bone growth in rats
Because GH drives skeletal growth in young animals, bone length is a practical readout for the GH axis. In a rat study, repeated Ipamorelin exposure was associated with an increased rate of longitudinal bone growth, assessed at the growth plate, along with changes in body weight (Johansen et al., 1999). The design used the GH axis as a functional endpoint rather than measuring receptor events directly.
Pharmacokinetic-pharmacodynamic modeling
Ipamorelin was also studied in a clinical pharmacology setting. Gobburu and colleagues fitted plasma concentration and GH response data from healthy volunteers to an indirect-response model, describing the relationship between exposure and GH release (Gobburu et al., 1999). The paper is mainly cited for its modeling approach and for documenting the peptide’s short plasma half-life.
Ghrelin receptor ligand design
Medicinal chemists studying GHS-R1a use Ipamorelin, GHRP-6, GHRP-2 and small molecules such as MK-677 as a comparison set. A 2007 review traces how peptide and non-peptide ligands evolved and where Ipamorelin fits among them (Moulin et al., 2007).
What the evidence does not show
- The selectivity claim rests largely on one company’s preclinical program, mainly the swine and rat experiments published in 1998. Independent replication of the full endocrine panel is limited.
- “Selective” refers to pituitary hormone outputs in those models. It does not mean Ipamorelin avoids other ghrelin receptor functions, such as effects on gut motility or appetite circuits, which were not the focus of the original work.
- The bone growth data come from young rats, a model that does not translate directly to mature animals or people.
- Clinical development for postoperative ileus was discontinued, and Ipamorelin has not been approved by any major regulator.
- Many statements about Ipamorelin online are extrapolated from ghrelin or other secretagogues rather than measured with Ipamorelin itself.
Regulatory status
Ipamorelin is not approved by the FDA. It has been evaluated in clinical studies, and development for postoperative ileus was discontinued. The World Anti-Doping Agency lists it under S2 (peptide hormones, growth factors, related substances and mimetics). Rogue Compounds sells it as a research reagent only.
Handling and storage in the lab
Store the lyophilized peptide sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Ipamorelin is made in small batches for Rogue Compounds. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is posted on the product page and in the COA Library.
View Ipamorelin on Rogue Compounds
References
- Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-561. PMID 9849822
- Johansen PB, et al. Ipamorelin, a new growth-hormone-releasing peptide, induces longitudinal bone growth in rats. Growth Horm IGF Res. 1999;9(2):106-113. PMID 10373343
- Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res. 1999;16(9):1412-1416. PMID 10496658
- Howard AD, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996;273(5277):974-977. PMID 8688086
- Moulin A, et al. Recent developments in ghrelin receptor ligands. ChemMedChem. 2007;2(9):1242-1259. PMID 17520591
- Isidro ML, Cordido F. Growth hormone secretagogues. Comb Chem High Throughput Screen. 2006;9(3):175-180. PMID 16533150
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.