Ipamorelin Research Standard
Ipamorelin (CAS 170851-70-4) is a synthetic pentapeptide, Aib-His-D-2-Nal-D-Phe-Lys-NH2, supplied as a 5 mg lyophilized powder in a 3 mL vial. It was identified within a series lacking the central Ala-Trp dipeptide of GHRP-1, and it earned the description “the first selective growth hormone secretagogue” for a specific, measurable reason rather than a marketing one.[1]
Mechanism of Action & Research Context
The molecular target is the growth hormone secretagogue receptor GHS-R1a, a class A G-protein-coupled receptor whose endogenous ligand is ghrelin, a peptide produced predominantly by the stomach.
What the selectivity actually is. In swine, GHRP-6 and GHRP-2 both raised plasma ACTH and cortisol. Ipamorelin did not — at doses more than 200-fold above its ED50 for GH release. None of the secretagogues tested affected FSH, LH, PRL or TSH. That single dissociation is what separates ipamorelin from the rest of the class and makes it the cleaner tool when a study needs GH-axis stimulation without a corticotropic confound.[1]
Potency comparable to GHRP-6. In primary rat pituitary cells, EC50 = 1.3 ± 0.4 nmol/L with Emax 85 ± 5%, against GHRP-6 at 2.2 ± 0.3 nmol/L and 100%. In anaesthetised rats, ED50 = 80 ± 42 nmol/kg against GHRP-6 at 115 ± 36. GHRP-2 is more potent but less efficacious (ED50 0.6 nmol/kg, Emax 56 ± 6 ng/mL in swine).[1]
Acts through the GHRP receptor, not GHRH. Profiling with GHRP and GHRH antagonists placed the response at the GHRP-like receptor.[1]
A shared pharmacophore. The peptidic secretagogues converge on the core Ala-Trp-(D-Phe)-Lys. Radio-competitive assay against radiolabelled ghrelin at GHSR1a has mapped which substitutions at positions 1, 2, 3 and 7 preserve or destroy binding across GHRP-1, GHRP-2, GHRP-6, hexarelin and ipamorelin — and confirmed that active metabolites, not only intact parent, retain receptor binding.[2]
An unusually constitutively active receptor. GHS-R1a is notable among GPCRs for high ligand-independent signalling. The interaction between the ligand-binding transmembrane domains and extracellular loop 2 appears partly responsible. That basal activity drives PLC, PKC and CRE signalling, is reversed by the inverse agonist [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P, and the receptor also shows C-terminal-dependent constitutive internalisation. A nonsense mutation (Ala204Glu) that alters only the constitutive activity is associated with familial short stature, which is the strongest evidence that the basal signalling matters rather than being an artefact.[3]
Part of the response may be indirect. Radiolabelled GHRPs accumulate in the glandular stomach, the site of ghrelin synthesis. Resecting the gastrointestinal tract attenuated the GH response to GHRP-6 by 60–70% while leaving the GHRH response intact, which points to endogenous ghrelin mediating a substantial share of the effect rather than the peptide acting on the pituitary alone.[4]
Research Applications
Primary fields of in vitro and preclinical laboratory investigation include:
Radio-competitive receptor binding assays against radiolabelled ghrelin at GHSR1a.[2]
GH release assays in primary pituitary cell culture, with GHRP and GHRH antagonists to establish which receptor is carrying the response.[1]
Constitutive-activity and inverse-agonist work at GHS-R1a.[3]
Structure-activity studies across the shared Ala-Trp-(D-Phe)-Lys core.[2]
Metabolite and analytical method development, where active metabolites retain receptor binding.[2]
Analytical Documentation
Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.
References
- Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552–561. doi:10.1530/eje.0.1390552
- Ferro P, Krotov G, Zvereva I, Rodchenkov G, Segura J. Structure-activity relationship for peptidic growth hormone secretagogues. Drug Test Anal. 2017;9(1):87–95. doi:10.1002/dta.1947
- Mear Y, Enjalbert A, Thirion S. GHS-R1a constitutive activity and its physiological relevance. Front Neurosci. 2013;7:87. doi:10.3389/fnins.2013.00087
- Ahnfelt-Rønne I, Nowak J, Olsen UB. Do growth hormone-releasing peptides act as ghrelin secretagogues? Endocrine. 2001;14(1):133–135. doi:10.1385/ENDO:14:1:133
- Locatelli V, Bresciani E, Bulgarelli I, et al. Ghrelin in gastroenteric pathophysiology. J Endocrinol Invest. 2005;28(9):843–848. doi:10.1007/BF03347579
Storage & Handling
Store at controlled room temperature, sealed and protected from light.
Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.
