Ipamorelin is a synthetic pentapeptide agonist at GHS-R1a, the ghrelin receptor, built from non-natural residues and capped with a C-terminal amide. It belongs to the growth hormone secretagogue series that grew out of the earlier growth hormone releasing peptides, and it is used in receptor binding, calcium mobilisation and arrestin recruitment assays as a selective GHS-R1a reference agonist. Ipamorelin is supplied by NuVion Health as a laboratory chemical for in vitro research use only.
Key facts
| Type / class | Synthetic pentapeptide, GHS-R1a agonist |
| Amino acid count | 5 |
| Molecular formula | C38H49N9O5 |
| Molecular weight | 711.9 g/mol |
| CAS number | 170851-70-4 |
| Synonyms | NNC 26-0161, ipamorelin acetate (salt form) |
| Supplied form | Lyophilised powder in a sealed vial |
Ipamorelin
$89 AUD
View productResearch use only. Not for human or veterinary use.
Structure and chemistry
The sequence is Aib-His-D-2-Nal-D-Phe-Lys-NH2. Only histidine and lysine are ordinary L-amino acids. Position 1 is alpha-aminoisobutyric acid, a quaternary residue with two methyl groups on the alpha carbon; position 3 is D-2-naphthylalanine, an extended aromatic side chain; and position 4 is D-phenylalanine. The C terminus is amidated.
Each of those features has a structural job. Aib strongly favours helical and turn geometry and removes the alpha proton, so the N terminus is conformationally restrained and resists aminopeptidase attack. The two D residues invert the backbone stereochemistry at positions 3 and 4, which blocks recognition by most mammalian endopeptidases and holds the two aromatic side chains in the arrangement the receptor pocket reads. The free lysine side chain and the amidated C terminus leave the molecule with net positive charge at neutral pH, which is why it dissolves readily in aqueous buffer. Ipamorelin shares no sequence with ghrelin, the endogenous ligand, and carries none of the Ser3 octanoyl modification that ghrelin needs; it is a peptidomimetic that reaches the same binding site through a different chemistry. The compound is usually supplied as the acetate salt, so the mass measured for the free peptide is what appears in identity work.
Mechanism of action
GHS-R1a is a class A G protein-coupled receptor encoded by GHSR, expressed in pituitary somatotroph cells and in defined hypothalamic and peripheral neuronal populations. The receptor is notable for high constitutive activity, signalling at around half its maximal level with no ligand bound, which makes it a standard system for studying inverse agonism as well as agonism. Ipamorelin binds the orthosteric pocket formed by the transmembrane bundle, with the D-2-Nal and D-Phe aromatics packing against residues in transmembrane helices 3, 6 and 7, and behaves as a full agonist in the assays used to characterise it.
Activation couples the receptor to Gq/11. The alpha subunit activates phospholipase C beta, which hydrolyses phosphatidylinositol 4,5-bisphosphate into inositol 1,4,5-trisphosphate and diacylglycerol. IP3 opens IP3 receptors on the endoplasmic reticulum and releases stored calcium into the cytosol, while diacylglycerol with that calcium activates protein kinase C. The calcium transient is the readout most commonly used in plate-based work. Downstream of the transient, calcium entry through voltage-gated channels and PKC activity converge on the exocytotic machinery in somatotroph cells, and the same receptor also recruits beta-arrestin 1 and 2 after GRK phosphorylation, giving receptor internalisation and a separate arrestin-dependent branch that can be measured independently of the G protein arm.
The pharmacological interest in this particular pentapeptide is its receptor selectivity. Across screening panels it activates GHS-R1a while leaving other secretagogue-adjacent receptors, including those upstream of corticotroph signalling, largely untouched, which is what distinguishes it from the earlier GHRP series. That property is why it is often chosen as the tool agonist when a GHS-R1a-specific signal has to be isolated from other pituitary receptor systems in the same preparation.
Research applications
- Competition binding assays at recombinant human GHS-R1a in membrane preparations, run against labelled ghrelin or small-molecule tracers.
- Calcium mobilisation assays in HEK293 or CHO lines stably expressing GHS-R1a, read on FLIPR-type instruments with fluorescent calcium indicators.
- IP-One accumulation assays measuring Gq pathway output, and NFAT reporter assays as a transcriptional readout of the same branch.
- Beta-arrestin recruitment and receptor internalisation assays using BRET, enzyme complementation or imaging formats, including work on the constitutive activity of the receptor.
- Primary rat pituitary cell culture, where the pentapeptide is applied as a selective agonist and the response compared with that of GHRH receptor ligands.
- RP-HPLC and LC-MS method development, where the naphthylalanine chromophore gives a distinctive ultraviolet signature.
On the NuVion catalogue the peptide sits in the Growth Hormones category with the other pituitary axis compounds.
Handling in the laboratory
The lyophilised solid is reconstituted with bacteriostatic water, added slowly down the vial wall with gentle swirling until fully dissolved. The reconstitution calculator converts a chosen solvent volume into the resulting concentration. Keep unopened vials sealed, dry, away from light and refrigerated as set out in the product documentation, and keep reconstituted solution refrigerated and use it within the period the documentation states. Short pentapeptides with aromatic side chains adsorb to untreated plastic at nanomolar working concentrations, so low-binding tubes or a carrier protein in the dilution buffer are worth using for concentration-response series. Material is characterised by RP-HPLC for purity and by mass spectrometry for identity.
Testing and supply from NuVion
NuVion Health has material independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity by mass spectrometry. Most batches are tested and the Certificate of Analysis for a tested batch is published on the product page, with the wider set held in the certificate of analysis library. Manufacture is GMP-audited, vials are supplied lyophilised and sealed, and orders are dispatched from within Australia.
Related compounds
Comparisons across the secretagogue series usually involve GHRP-2, an earlier and less selective GHS-R1a agonist, and CJC-1295 No DAC, which acts at the separate GHRH receptor and lets Gq and Gs signalling be compared side by side.
Frequently asked questions
What is Ipamorelin used for in research?
It is used as a selective agonist at the ghrelin receptor GHS-R1a in binding, calcium mobilisation, IP-One and arrestin recruitment assays. Its selectivity makes it useful when a GHS-R1a signal has to be separated from other receptor systems present in the same cells.
How does Ipamorelin differ from GHRH analogues?
They act at different receptors. Ipamorelin binds GHS-R1a, a class A receptor coupled to Gq, so the immediate readout is a calcium transient. GHRH analogues such as sermorelin bind the class B GHRH receptor coupled to Gs, where the readout is cAMP accumulation.
Is Ipamorelin a therapeutic good in Australia?
No. It is supplied here as a laboratory chemical. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration. It is sold for in vitro laboratory research and for no other purpose.
How should Ipamorelin be stored?
Keep the sealed vial of lyophilised powder dry, away from light and refrigerated as described in the product documentation. After reconstitution, keep the solution refrigerated and use it within the period stated there. Aliquoting stock solutions limits repeated freeze-thaw of the same material.
Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
