Research Use Only — Not for Human Consumption. All content below is intended exclusively for qualified laboratory researchers. Nothing on this page is medical advice, and no product discussed is intended for human or veterinary use.
Introduction
Hexarelin (INN examorelin; codes EP-23905, MF-6003, Mediolanum Farmaceutici) is a synthetic hexapeptide of the growth hormone secretagogue family, derived from GHRP-6 with higher potency and metabolic stability. A compact, well-characterized ligand for GHS-R1a (the ghrelin receptor) — a Gq-coupled system complementary to the Gs-coupled GHRH receptor pathway, enabling clean dissection of somatotroph signaling and GPCR selectivity in vitro.
Molecular Structure
His–D-2-Me-Trp–Ala–Trp–D-Phe–Lys–NH2. CAS 140703-51-1, C47H58N12O6, 887.04 g/mol (PubChem CID 6918297). Two D-amino acids (peptidase resistance), C-terminal amidation, aromatic-rich core (positions 2, 4, 5) as the GHS pharmacophore, charged His/Lys anchors. Straightforward to synthesize at high purity.
The Receptor: From GHS-R Cloning to Ghrelin
GHS-R cloned 1996 (Howard et al., Science); ghrelin identified 1999 (Kojima et al., Nature) as the endogenous ligand. Hexarelin is a synthetic, non-ghrelin-sequence agonist at the ghrelin receptor — ideal for mapping ligand recognition without ghrelin’s octanoyl modification.
Intracellular Signaling in Cell Models
GHS-R1a is Gq/11-coupled: PLC activation → IP3 + DAG → intracellular Ca2+ transients (standard functional readout) + PKC activation. Distinct from the Gs–cAMP pathway of GHRH analogs; radioligand displacement assays give the complementary Ki binding dataset.
In Vitro Study Applications
receptor selectivity and SAR screening (aromatic positions 2, 4, 5); pituitary somatotroph cell models (Ca2+ mobilization alongside GHRH-analog responses); cardiovascular cell models (reported CD36 interactions, strictly binding/signaling level); biased-signaling and desensitization studies (internalization, recycling, G-protein vs β-arrestin); analytical reference work (D/L epimer resolution, amidated vs free-acid C-termini).
Analytical Characterization
RP-HPLC (214/280 nm UV), ESI-MS (monoisotopic 886.46 Da), amino acid analysis (D-2-Me-Trp hydrolysis conditions), chiral verification of D-positions; lyophilized acetate/TFA salt, –20°C storage; tryptophan oxidation risk, light-protected storage.
Literature Context
Bowers CY et al., Endocrinology. 1984;114(5):1537–1545; Deghenghi R et al., Life Sci. 1994;54:1321–1328; Howard AD et al., Science. 1996;273(5277):974–977; Kojima M et al., Nature. 1999;402(6762):656–660.
Conclusion
small, stable, selective, mechanistically transparent probe for Gq–PLC–Ca2+ signaling at the ghrelin receptor; strictly for qualified laboratory research with analytically verified samples.
Research Use Only — Not for Human Consumption. This material is for qualified laboratory researchers and describes laboratory applications only. It contains no medical, therapeutic, dosing, or reconstitution guidance, and no product described here is intended for human or veterinary use.