Key findings
- The peptide is Aib-His-D-2-Nal-D-Phe-Lys-NH2, identified within a chemistry series that lacks the central Ala-Trp dipeptide of growth hormone releasing peptide 1. [1]
- In primary rat pituitary cells it released growth hormone with an EC50 of 1.3 nmol/l and an efficacy of 85 percent of the GHRP-6 maximum, and antagonist profiling placed the response at a GHRP-like receptor rather than the growth hormone releasing hormone receptor. [1]
- In pancreatic tissue fragments from normal and streptozotocin-diabetic rats it evoked insulin release across 10 to the minus 12 through 10 to the minus 6 molar, and a calcium channel blocker or adrenergic antagonists reduced that release. [2]
- The pentapeptide backbone has been reused for fluorine-18 labeled and boron-rich ghrelin receptor ligands, with binding and activation measured for those derivatives rather than for the parent peptide. [3][4]
Identity and structure
- Sequence
- Aib-His-D-2-Nal-D-Phe-Lys-NH2 [1]
- Class
- A pentapeptide growth hormone secretagogue found in a series lacking the Ala-Trp dipeptide of growth hormone releasing peptide 1 [1]
- Receptor in cited assays
- Responses in primary rat pituitary cells were blocked by GHRP antagonists and not by growth hormone releasing hormone antagonists [1]
- Form as supplied
- Sterile lyophilized powder
Mechanism as studied
The discovery study separated the two pituitary pathways with GHRP and growth hormone releasing hormone antagonists and concluded that the pentapeptide acts through a GHRP-like receptor. In swine the same work found no change in follicle stimulating hormone, luteinizing hormone, prolactin or thyroid stimulating hormone, and no rise in adrenocorticotropic hormone or cortisol, in contrast to GHRP-6 and GHRP-2. [1]
In ex-vivo pancreatic tissue the insulin response was reduced by a calcium channel blocker and by adrenergic antagonists, which the authors read as calcium channel and adrenergic receptor involvement rather than a direct secretory action. [2]
Research findings
In vitro
- System
- Primary rat pituitary cells, with GHRP and growth hormone releasing hormone antagonists applied to separate the two receptor pathways
- Measured
- Growth hormone release potency and efficacy relative to GHRP-6, receptor pathway by antagonist blockade
- Reported
- EC50 was 1.3 plus or minus 0.4 nmol/l with an efficacy of 85 plus or minus 5 percent, against 2.2 plus or minus 0.3 nmol/l for GHRP-6. Antagonist profiling indicated a GHRP-like receptor. [1]
Preclinical in vivo
- System
- Pentobarbital anaesthetised rats and conscious swine, compared against GHRP-6 and GHRP-2
- Measured
- Growth hormone release, plasma follicle stimulating hormone, luteinizing hormone, prolactin, thyroid stimulating hormone, adrenocorticotropic hormone and cortisol
- Reported
- Growth hormone release was comparable in potency and efficacy to GHRP-6 in both species. None of the secretagogues changed follicle stimulating hormone, luteinizing hormone, prolactin or thyroid stimulating hormone. Unlike GHRP-6 and GHRP-2, the pentapeptide did not raise adrenocorticotropic hormone or cortisol above the levels seen with growth hormone releasing hormone stimulation. [1]
Ex vivo
- System
- Pancreatic tissue fragments removed from normal and streptozotocin-diabetic rats and incubated with the peptide, with diltiazem, yohimbine, propranolol or atropine
- Measured
- Insulin release by radioimmunoassay across 10 to the minus 12 through 10 to the minus 6 molar
- Reported
- The peptide increased insulin secretion from both normal and diabetic pancreas. Diltiazem, yohimbine, propranolol or a combination inhibited that secretion. Atropine reduced it in diabetic but not in normal tissue. [2]
Ex vivo
- System
- Pituitary cell cultures from young female rats that had previously received the peptide, growth hormone releasing hormone or saline over 21 days
- Measured
- Somatotroph ultrastructure and secretion granule volume density, percentage of somatotroph cells, ratio of strongly to weakly staining growth hormone cells, intracellular growth hormone content
- Reported
- Ultrastructure did not change but secretion granule volume density increased after prior exposure to either peptide. In cultures from the peptide group, a 4 h exposure to the peptide, to GHRP-6 or to growth hormone releasing hormone at 10 nanomolar raised the percentage of somatotrophs and intracellular growth hormone content without changing the strongly to weakly staining ratio. [5]
In vitro
- System
- A series of NN703 analogues combining lysine mimetics with naphthylalanine or biphenylalanine cores, assayed in a rat pituitary cell based assay; the tested compounds are hybrids rather than the catalog pentapeptide
- Measured
- Growth hormone releasing potency in the cell assay and in pigs
- Reported
- Re-introducing C-terminal pharmacophores that an earlier optimisation had removed produced compounds that were unexpectedly potent both in the cell assay and in pigs. [6]
In vitro
- System
- 4-fluorobenzoylated growth hormone secretagogue derivatives built from GHRP-1, GHRP-2, GHRP-6, G-7039 and the catalog pentapeptide; the assayed compounds are labeled analogues rather than the parent peptides
- Measured
- Ghrelin receptor binding affinity and functional efficacy, radiochemical yield, radiochemical purity and molar activity
- Reported
- The G-7039 derived analogue carried a binding affinity of 69 nM and an efficacy of 1.1 nM and was the most suitable for fluorine-18 labeling. Prosthetic group labeling gave an average decay-corrected radiochemical yield of 48 percent at radiochemical purity of 99 percent or better. [3]
Handling for in-vitro work
Open questions
- No cited study resolves a structure of the pentapeptide bound to the secretagogue receptor, so the binding pose is inferred from antagonist blockade rather than observed.
- Every cited study examines the single peptide; none describes the composition, stability or constituent interaction of a mixture containing it.
Human studies of this pentapeptide exist and concern finished formulations; they are out of scope for a research material profile.
Lot records
Check the record for the exact material you order. A published paper and a batch certificate answer different questions.
- RV-24-0037-2 ↗Ipamorelin · 99.40% HPLC2026-09-22
- RV-24-0037-1 ↗Ipamorelin · 99.40% HPLC2026-09-16
References
- Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. European journal of endocrinology. 1998.
- Adeghate E, Ponery AS Mechanism of ipamorelin-evoked insulin release from the pancreas of normal and diabetic rats. Neuro endocrinology letters. 2004.
- Fowkes MM, Lalonde T, Yu L, et al. Peptidomimetic growth hormone secretagogue derivatives for positron emission tomography imaging of the ghrelin receptor. European journal of medicinal chemistry. 2018.
- Worm DJ, Els-Heindl S, Kellert M, et al. A stable meta-carborane enables the generation of boron-rich peptide agonists targeting the ghrelin receptor. Journal of peptide science : an official publication of the European Peptide Society. 2018.
- Jiménez-Reina L, Cañete R, de la Torre MJ, et al. Influence of chronic treatment with the growth hormone secretagogue Ipamorelin, in young female rats: somatotroph response in vitro. Histology and histopathology. 2002.
- Hansen TK, Ankersen M, Raun K, et al. Highly potent growth hormone secretagogues: hybrids of NN703 and ipamorelin. Bioorganic & medicinal chemistry letters. 2001.
Publication records fetched from PubMed on 2026-09-20. Profile text reviewed 2026-09-20.