Ipamorelin is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, developed as a selective agonist of the growth hormone secretagogue receptor GHS-R1a — the same receptor engaged by the endogenous hormone ghrelin. It is a very small molecule for its class, about 712 g/mol, and almost every residue in it is non-standard: an unnatural aminoisobutyric acid at the N-terminus, two D-amino acids in the middle, and a C-terminal amide. That is not decoration. Each modification exists to resist proteolysis or to lock the conformation that the receptor recognises, and together they turn five residues into a stable, orally-inspired scaffold.
What made ipamorelin notable when it was described in the late 1990s was selectivity. Earlier secretagogues in the GHRP series were reported to move cortisol, prolactin and appetite signalling alongside growth hormone; ipamorelin was characterised as producing a comparatively clean growth hormone response in animal models, which is why it became a standard tool compound. Ipamorelin is supplied here for laboratory research use only.
Ipamorelin at a glance
| Property | Value |
|---|---|
| Sequence | Aib-His-D-2-Nal-D-Phe-Lys-NH2 |
| Length | 5 residues, C-terminally amidated |
| Non-standard residues | Aib (2-aminoisobutyric acid), D-2-naphthylalanine, D-phenylalanine |
| CAS number | 170851-70-4 |
| Molecular formula | C38H49N9O5 |
| Molecular weight | 711.85 g/mol |
| Receptor | GHS-R1a (ghrelin receptor), class A GPCR |
| Signalling | Gq → phospholipase C → IP3 / DAG → intracellular calcium |
| Reported selectivity | Growth hormone release without notable cortisol or prolactin movement in animal models |
| Sizes supplied | 2 mg, 5 mg, 10 mg lyophilized vials |
| Purity specification | ≥99% by RP-HPLC with lot-matched COA |
Origin and structure: five residues, four modifications
The growth hormone secretagogue series began with peptides derived from met-enkephalin analogues, which released growth hormone through a receptor that GHRH antagonists could not block. That observation implied a distinct receptor, which was cloned in 1996 as GHS-R1a; ghrelin was identified as its endogenous ligand in 1999. Ipamorelin came out of the medicinal chemistry effort that ran alongside this work, with the explicit aim of improving selectivity over earlier compounds.
Its structure reflects that effort residue by residue. Aib at position 1 is 2-aminoisobutyric acid, an alanine with a second methyl group on the alpha carbon; it strongly favours helical and turn conformations and is not a substrate for aminopeptidases, so it stabilises both the shape and the N-terminus. D-2-naphthylalanine at position 3 supplies a large bicyclic aromatic side chain in a D configuration — bulk for hydrophobic receptor contact, and stereochemistry that ordinary proteases do not recognise. D-phenylalanine at position 4 repeats the trick with a smaller aromatic ring. The C-terminal amide on the lysine removes the terminal negative charge, which in this receptor family is associated with improved binding.
The result is a peptide that is nominally five residues long but chemically closer to a small molecule: compact, protease-resistant and conformationally constrained. At 711.85 g/mol it is the lightest peptide in the growth hormone section of this catalogue, roughly one-fifth the mass of sermorelin, which has direct consequences for molar comparisons.
How ipamorelin is thought to work
Ipamorelin binds GHS-R1a, a class A G protein-coupled receptor expressed on pituitary somatotrophs and in the hypothalamus. Unlike the GHRH receptor, which couples to Gs and cyclic AMP, GHS-R1a couples predominantly to Gq: phospholipase C activation, inositol trisphosphate and diacylglycerol production, and a rise in intracellular calcium that triggers secretory granule release. It also shows high constitutive activity in the absence of ligand, a property that makes it a favourite system in inverse-agonist pharmacology.
Because the two receptor systems use different second messengers on the same cell, GHRH receptor agonists and GHS-R1a agonists are studied together constantly, and their combination has been reported as more than additive in several models. A second reported mechanism contributes: secretagogue receptor activation is associated with suppression of somatostatin tone, which removes an inhibitory brake at the same time as the stimulatory signal is applied.
Selectivity is the property most often cited for ipamorelin, and it deserves precise framing. Published animal work reported growth hormone release without the increases in ACTH, cortisol and prolactin seen with GHRP-6 and hexarelin at comparable growth-hormone-releasing potencies. This is a comparative pharmacological observation from specific models, not a guarantee of a clean profile in every system, and it is the reason ipamorelin is used to isolate GHS-R1a signalling from the wider neuroendocrine background.
What research has examined
Receptor pharmacology
Ipamorelin is used as a reference agonist in GHS-R1a binding assays, calcium flux and inositol phosphate accumulation assays, and in work characterising the receptor's constitutive activity and its biased signalling. This is arguably its primary role.
Comparative secretagogue studies
It is the standard selectivity comparator against which the older GHRPs are measured, appearing in almost every study that ranks the class. Direct comparisons are set out in ipamorelin vs GHRP-2 and ipamorelin vs GHRP-6.
Gastrointestinal motility models
Ghrelin receptor agonists have been examined in gastric emptying and postoperative ileus models in animals, a strand of work distinct from the endocrine literature and one where ipamorelin was investigated clinically at an early stage without reaching approval.
Combination designs
Pairing with a GHRH receptor agonist is the most common experimental design in this space; pre-blended research material exists as CJC-1295 with ipamorelin. Any such study should state both molar concentrations rather than a combined mass, because the two peptides differ in molecular weight by nearly a factor of five.
Forms and sizes we supply
Ipamorelin is stocked as a lyophilized powder in 2 mg (USD 40), 5 mg (USD 50) and 10 mg (USD 75) sealed vials. The molar arithmetic favours it heavily: at 711.85 g/mol, a 5 mg vial contains approximately 7.02 micromoles, nearly five times the molar content of a 5 mg vial of a GHRH analogue. Anyone comparing a secretagogue with a GHRH analogue on a milligram basis is not running a controlled comparison. The class sits under GHRPs and secretagogues.
Reconstitution and storage in a laboratory context
The calculation: a 5 mg vial reconstituted with 2 mL of bacteriostatic water gives 2.5 mg/mL, equivalently 2,500 mcg/mL; 0.1 mL (10 units on a U-100 syringe) contains 250 mcg. In molar terms the stock is approximately 3.51 mM — a high figure by peptide standards, and one that requires a long serial dilution to reach the nanomolar concentrations used in receptor assays.
Ipamorelin is among the more robust peptides to handle. It contains no cysteine, no methionine and no asparagine-glycine motif, so the disulfide scrambling, oxidation and deamidation problems that dominate stability discussions elsewhere do not apply. The two large aromatic side chains make it somewhat less hydrophilic than its size suggests, so allow the cake to dissolve fully and inspect for clarity rather than assuming instant solubility. Lyophilized vials are stored at −20 °C protected from light and moisture; reconstituted solution is refrigerated and aliquoted. General guidance is in the peptide storage guide.
Purity, COA and how to read one
Each lot is purified by reversed-phase HPLC to at least 99% with mass confirmation and a lot-matched certificate. Two checks are specific to this peptide. First, confirm the mass against 711.85 g/mol for the amidated pentapeptide; a value about 1 Da higher indicates the free acid rather than the amide, which is a different molecule pharmacologically. Second, be aware of what the certificate cannot establish: the D configuration at positions 3 and 4 and the Aib at position 1 are invisible to mass spectrometry, since enantiomers are isobaric. A D-to-L epimer would show the correct mass and could elute close to the target. Confidence in stereochemistry rests on synthesis documentation, on chromatographic resolution good enough to show a single symmetrical peak, and where required on dedicated chiral analysis. Our COA reading guide explains what each analytical section does and does not prove.
Regulatory status
Ipamorelin has no marketing authorisation as a medicine in the United States or elsewhere; early clinical investigation in gastrointestinal motility did not lead to approval. It is not a dietary supplement ingredient and not a generally available compounded medication. Material supplied here is research use only, for in-vitro and preclinical laboratory investigation by qualified researchers, and is not intended for human or veterinary administration.
Related peptides and further reading
Within the secretagogue class, GHRP-2 and GHRP-6 are the older hexapeptides against which ipamorelin's selectivity was defined, and hexarelin is the more potent but less selective relative. On the other side of the axis, sermorelin, Modified GRF 1-29 and tesamorelin act at the GHRH receptor through an entirely different second-messenger system. The whole landscape is mapped in the GH secretagogue landscape explained.