Ipamorelin: Receptor Selectivity, Chemistry and Published Assay Data

Ipamorelin is a C-terminally amidated pentapeptide first described by Raun and colleagues at Novo Nordisk in 1998 under the development code NNC 26-0161. Its five residues are 2-aminoisobutyric acid, L-histidine, D-2-naphthylalanine, D-phenylalanine and L-lysine, giving the formula C38H49N9O5 and a molecular weight of 711.9 g/mol.

Three of the five positions are non-proteinogenic. Position 1 carries 2-aminoisobutyric acid, a quaternary alpha-methylated glycine that constrains backbone conformation, and positions 3 and 4 carry D-configured aromatic residues, D-2-naphthylalanine and D-phenylalanine. The C-terminus is an amide rather than a free acid. Each of these features is a departure from ordinary L-amino-acid peptide chemistry, and together they are why the molecule survives peptidase exposure long enough to be measurable in circulation.

The 1998 paper describes how the compound was found. Its authors were working through a series that lacked the central dipeptide of GHRP-1, and ipamorelin emerged from that series as the member combining high growth hormone releasing potency with an unusually narrow hormonal footprint. The molecule therefore has a documented structural lineage within the growth hormone releasing peptide family rather than an independent origin. PubChem lists its exact and monoisotopic mass as 711.3857 Da and its XLogP as 1.8.

Ipamorelin acts as an agonist at the growth hormone secretagogue receptor 1a (GHS-R1a), a class A G protein-coupled receptor whose endogenous ligand is acyl-ghrelin. In primary rat pituitary cells the compound released growth hormone with an EC50 of 1.3 nM, and in BHK cells expressing the receptor it drove inositol trisphosphate accumulation with an EC50 of 46.9 nM.

The gap between those two numbers is informative: growth hormone release from a native pituitary cell is roughly thirty-six-fold more sensitive than a second-messenger readout in a recombinant fibroblast line, the signature of signal amplification downstream of receptor occupancy. Raun and colleagues also showed pharmacologically that the compound acts through a GHRP-like receptor rather than the growth hormone releasing hormone receptor.

No cryo-electron microscopy structure of ipamorelin bound to GHS-R1a has been published. What exists is a body of structural work on the receptor with other agonists, and the most recent of it is directly relevant. Wang and colleagues reported structures of GHSR in complex with Gq proteins bound to macimorelin at 2.63 angstroms and anamorelin at 2.52 angstroms in 2025. Both ligands occupied a bifurcated binding pocket split by a conserved salt bridge between E124 (3.33) and R283 (6.55).

A 2025 review by Polishchuk and colleagues synthesized that structural picture, describing recent cryo-electron microscopy structures as revealing a bipartite binding pocket that frames biased signalling and constitutive receptor activity, and distinguishing acyl-ghrelin as the high-potency agonist from des-acyl ghrelin, which predominates in circulation at low potency.

Ipamorelin was designated the first selective growth hormone secretagogue because, in conscious swine, it released growth hormone without changing FSH, LH, prolactin or TSH, and without raising ACTH or cortisol beyond what growth hormone releasing hormone itself produced. That separation held at exposure levels 200-fold above the ED50 for growth hormone release.

The comparison that gives the claim its force is internal to the same study. GHRP-6 and GHRP-2, tested alongside, did raise ACTH and cortisol. All three peptides act through the same receptor class, so the difference is not receptor identity but ligand structure. That is the defining published property of this molecule and the reason its name carries the word selective in the original title.

Selectivity here describes one measured hormone panel in one species. The 1998 panel covered FSH, LH, prolactin, TSH, ACTH and cortisol, and endpoints outside it were never part of the claim. Gouda and Ganesh reported in 2024 that cichlid fish given 5 or 30 µg of ipamorelin acetate over 21 days showed raised serum luteinizing hormone and 11-ketotestosterone, a teleost result sitting outside that mammalian panel.

Reviews published in 2026 continue to place the compound within the growth hormone secretagogue class rather than as an outlier. Dominikowski and colleagues stratified growth hormone releasing hormone analogues, growth hormone secretagogues including ipamorelin, and IGF-1 variants by evidence tier, and contrasted the peer-reviewed pharmacology against protocols circulated online.

Ipamorelin has been examined in rats, swine, ferrets and fish. The reported endpoints cluster into three groups: longitudinal bone growth in adult female rats, gastrointestinal motility in rodent and ferret preparations, and hypothalamic-pituitary-testicular signalling in a cichlid. Each result below is stated in the species and preparation where it was measured.

On bone, Johansen and colleagues gave adult female rats 0, 18, 90 or 450 µg per day, split across three daily applications for 15 days, and measured longitudinal growth rate as the distance between intravital tetracycline bands laid down on days 0, 6 and 13 in the proximal tibial metaphysis. The rate rose from 42 µm per day in the vehicle group to 44, 50 and 52 µm per day across the three ascending exposure levels, with P less than 0.0001.

On gastrointestinal motility, Venkova and colleagues used a rat model of postoperative ileus in which fasted males underwent laparotomy with intestinal manipulation. A single 1 mg/kg exposure by infusion shortened the time to first bowel movement relative to vehicle. A repeated regimen at 0.1 or 1 mg/kg significantly increased cumulative fecal pellet output over 48 hours, whereas the single exposure did not.

Lu and colleagues added a direct enteric measurement in 2024. Working with isolated ferret ileum, they compared inhibition of contractions evoked by electrical field stimulation and found ipamorelin inhibited them by 54.4 percent against 94.4 percent for anamorelin. The two GHS-R1a agonists therefore separate cleanly on a tissue-level endpoint that requires no intact endocrine axis.

In the cichlid Oreochromis mossambicus, Gouda and Ganesh reported that both 5 µg and 30 µg exposures over 21 days raised counts of primary spermatocytes, secondary spermatocytes and early spermatids relative to controls, alongside raised serum luteinizing hormone and 11-ketotestosterone. Only the 30 µg level raised late spermatid counts and androgen receptor protein expression, giving a two-point separation between the exposure levels.

Ipamorelin has one published human pharmacokinetic and pharmacodynamic modelling study. Gobburu and colleagues used five infusion rates with eight healthy volunteers at each rate and reported a terminal half-life of 2 hours, a clearance of 0.078 L/h/kg and a steady-state volume of distribution of 0.22 L/kg, with kinetics proportional across the range studied.

The pharmacodynamic side of that work is equally specific. Growth hormone rose as a single episode peaking at 0.67 hours and then declining exponentially. Fitting an indirect response model gave an SC50 of 214 nmol/L and a maximal growth hormone production rate of 694 mIU/L/h. Between-individual variability was larger for the pharmacodynamic parameters than for the pharmacokinetic ones, meaning circulating concentrations were more predictable than the hormonal response they produced.

A steady-state volume of distribution of 0.22 L/kg sits close to extracellular fluid volume, the signature of a small polar peptide that does not partition into tissue. Metabolic fate has been mapped separately. Thomas and colleagues profiled the growth hormone releasing peptide class across rat in vivo samples and human serum in vitro and identified 28 metabolites overall, at least three for each peptide, arising from exopeptidase, amidase and endopeptidase activity. That metabolite panel, rather than the parent peptide alone, is what analytical laboratories screen against.

Ipamorelin is identified by its exact mass of 711.3857 Da, its InChIKey NEHWBYHLYZGBNO-BVEPWEIPSA-N and CAS number 170851-70-4. Laboratories separate it by reversed-phase liquid chromatography and confirm it by high-resolution tandem mass spectrometry, the standard approach for small C-terminally amidated peptides below 2 kDa.

Two features make that confirmation straightforward. The D-2-naphthylalanine residue gives strong ultraviolet absorbance and a distinctive fragment, and the C-terminal amide shifts the parent mass by one dalton relative to the free acid, so amide loss is directly visible in the mass spectrum. Purity is conventionally reported as area percent by HPLC.

Coutinho and colleagues, reviewing peptide and peptide-analogue drugs in 2026, reported that the largely unregulated supply chain leaves products often mislabeled or contaminated, and that analytical detection remains difficult because these peptides resemble endogenous hormones structurally and have short half-lives. Independent lot-level confirmation by chromatography and mass spectrometry is the only way to close that gap for a given batch.

For literature searching, note that the discovery-era record was published under the development code NNC 26-0161, so a search on the common name alone will miss part of it.

Published handling figures for ipamorelin come from supplier specifications rather than from peer-reviewed measurement. Suppliers describe the acetate salt as a white to off-white lyophilized solid at 98 percent or higher purity by HPLC, stored at minus 20 degrees Celsius, and shipped at ambient temperature within the continental United States.

Reported solubility for the acetate is 20 mg/mL in dimethylformamide, 20 mg/mL in dimethyl sulfoxide, 30 mg/mL in ethanol and 10 mg/mL in phosphate-buffered saline at pH 7.2. Those are supplier specifications, and the aqueous figure is the one most relevant to buffer work. A computed XLogP of 1.8 is consistent with a peptide that dissolves in aqueous buffer without requiring an organic co-solvent.

Salt form matters for documentation. CAS number 170851-70-4 and PubChem CID 9831659 describe the free peptide with formula C38H49N9O5 and molecular weight 711.9 g/mol. Suppliers commonly ship the acetate, which carries a variable acetate component and therefore a different measured mass per vial. Records should state which form the material is, because peptide content by weight differs between them.

Two chemical features bear on storage. The C-terminal amide can hydrolyse to the free acid, a one-dalton shift detectable by mass spectrometry and the most useful degradation marker for this molecule. The lysine side-chain amine is the reactive handle most likely to participate in unwanted acylation.