Overview
Hexarelin (also known by the CAS number 140703-51-1 and the name Examorelin) is a synthetic hexapeptide belonging to the growth hormone secretagogue (GHS) family of peptides. It was developed as a research analog of ghrelin, a naturally occurring hormone, and works by binding to the growth hormone secretagogue receptor type 1a (GHS-R1a). With a molecular weight of approximately 887 Da and the formula C47H58N12O6, it is composed of six amino acid residues, including modified versions of tryptophan and phenylalanine that distinguish it from naturally occurring peptides. Hexarelin has been investigated in laboratory and preclinical research settings for its interactions with receptor signaling pathways, and published studies have explored topics ranging from neuroprotection in retinal cell models to its potential role in modulating inflammatory responses. Like all research peptides, Hexarelin is intended strictly for scientific research purposes and is not approved for human use or consumption.
Research & Bioactivity
Hexarelin is a synthetic growth hormone secretagogue that researchers have studied primarily in relation to its activity at the growth hormone secretagogue receptor type 1a (GHS-R1a), through which it promotes endogenous growth hormone release. Studies have examined its potential neuroprotective properties, including animal model research investigating the survival of retinal ganglion cells following optic nerve injury, suggesting areas of interest in neuroprotection research. Research has also investigated hexarelin in the context of organ protection, with studies using ischemia/reperfusion injury models to explore its effects on acute kidney injury and the molecular pathways involved, including the MDM2/p53 apoptosis pathway. Additional research has explored hexarelin's interactions with CD36 receptors, which has drawn interest in studies examining inflammatory responses in animal models. Researchers have further studied hexarelin's physicochemical behavior in the context of oral peptide delivery, using molecular dynamics simulations to understand how it interacts with permeation enhancers and bile salts in intestinal environments.
Published Research
Hexarelin promotes the survival of retinal ganglion cells after optic nerve transection.
Chow KBS — 2026
OBJECTIVE: Hexarelin is a growth hormone secretagogue receptor type 1a agonist with a potent anti-apoptotic effect. We studied the neuroprotective effect of hexarelin on the survival of retinal ganglion cells (RGCs) in the retina following optic nerve transection (ONT). MATERIALS AND METHODS: Golden hamsters of 8-9 weeks old were used. For 7 days following ONT with one dose of drug, hamsters were injected with single dose of saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin daily for 5 days. For 7 days after ONT with two doses of drugs, saline, 100 μg/kg and 150 μg/kg hexarelin were injected twice daily for 5 days. Survival of RGCs was quantified by immunostaining with Tuj1 antibody in retina whole mount. RESULTS: Single daily doses of 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin dose dependently and significantly increased the survival of RGC. The survival rates of RGC in saline, 25 μg/kg, 50 μg/kg, and 100 μg/kg hexarelin-treated hamsters were 51.2%, 62.4%, 68.5%, and 74.6%, respectively, in 7 days ONT. Two daily doses of saline, 100 μg/kg and 150 μg/kg hexarelin promoted survivals to 72.9%, 91.4%, and 109.2%, respectively, in 7 days ONT. CONCLUSIONS: Single daily doses of hexarelin dose dependently increased the survival of RGC. Two daily doses of hexarelin increased RGC survival further and 150 μg/kg hexarelin twice daily is optimal for the survival of RGC.
Identification of alexamorelin consumption biomarkers using human hepatocyte incubations and high-resolution mass spectrometry.
Pobee E, Daziani G, Gameli PS, Basile G, Carlier J, et al. — 2025
Alexamorelin is a synthetic peptide and growth hormone secretagogue (GHS) with potential performance-enhancing properties, making its use and abuse a topic of interest in clinical research and doping monitoring. Alexamorelin mimics the natural peptide hormone ghrelin by binding to the GHS type 1a receptor (GHS-R1a) in the pituitary gland, thereby promoting endogenous growth hormone release. Identifying alexamorelin and/or its metabolite biomarkers is crucial for effective doping controls. The purpose of this study was to determine and characterize biomarkers associated with alexamorelin intake. In silico metabolite predictions were performed using GLORYx freeware, and in vitro incubations were conducted with pooled human hepatocytes from 10 donors. Samples were analysed using liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS), with data processed through Thermo Scientific's Compound Discoverer. GLORYx predicted 21 single-reaction metabolites. N-Acetylation was identified as the primary transformation, with the highest probability score (98%), and occurring either at the C-terminal Ala or the N-terminal Lys. Other predicted transformations included N-oxidation, hydroxylation, amide hydrolysis, oxidative deamination, and phase II N-glucuronidation, with probability scores below 40%. All these transformations were predicted to occur at the two C-terminal (Ala or His) or N-terminal (d-Phe or Lys) amino acids. After 3 h of incubation with hepatocytes, only one metabolite (known as examorelin or hexarelin) was detected, resulting from the C-terminal cleavage of the Ala amino acid; this metabolic reaction is mediated by a carboxypeptidase. The alexamorelin signal decreased approximately 150-fold after 3 h, indicating significant hepatic metabolism. However, examorelin itself is a commercially available GHS secretagogue, and thus, it is not specific to alexamorelin consumption. Detecting alexamorelin remains critical to documenting its use.
Pharmacological targeting of the hyper-inflammatory response to SARS-CoV-2-infected K18-hACE2 mice using a cluster of differentiation 36 receptor modulator.
Gauvin J, Huynh DN, Dubuc I, Lê C, Tugores R, et al. — 2024
The scientific and medical community faced an unprecedented global health hazard that led to nearly 7 million deaths attributable to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In spite of the development of efficient vaccines against SARS-CoV-2, many people remain at risk of developing severe symptoms as the virus continues to spread without beneficial patient therapy. The hyper-inflammatory response to SARS-CoV-2 infection progressing to acute respiratory distress syndrome remains an unmet medical need for improving patient care. The viral infection stimulates alveolar macrophages to adopt an inflammatory phenotype regulated, at least in part, by the cluster of differentiation 36 receptor (CD36) to produce unrestrained inflammatory cytokine secretions. We suggest herein that the modulation of the macrophage response using the synthetic CD36 ligand hexarelin offers potential as therapy for halting respiratory failure in SARS-CoV-2-infected patients.
Revealing the interaction between peptide drugs and permeation enhancers in the presence of intestinal bile salts.
Hossain S, Kneiszl R, Larsson P — 2023
Permeability enhancer-based formulations offer a promising approach to enhance the oral bioavailability of peptides. We used all-atom molecular dynamics simulations to investigate the interaction between two permeability enhancers (sodium caprate, and SNAC), and four different peptides (octreotide, hexarelin, degarelix, and insulin), in the presence of taurocholate, an intestinal bile salt. The permeability enhancers exhibited distinct effects on peptide release based on their properties, promoting hydrophobic peptide release while inhibiting water-soluble peptide release. Lowering peptide concentrations in the simulations reduced peptide-peptide interactions but increased their interactions with the enhancers and taurocholates. Introducing peptides randomly with enhancer and taurocholate molecules yielded dynamic molecular aggregation, and reduced peptide-peptide interactions and hydrogen bond formation compared to peptide-only systems. The simulations provided insights into molecular-level interactions, highlighting the specific contacts between peptide residues responsible for aggregation, and the interactions between peptide residues and permeability enhancers/taurocholates that are crucial within the mixed colloids. Therefore, our results can provide insights into how modifications of these critical contacts can be made to alter drug release profiles from peptide-only or mixed peptide-PE-taurocholate aggregates. To further probe the molecular nature of permeability enhancers and peptide interactions, we also analyzed insulin secondary structures using Fourier transform infrared spectroscopy. The presence of SNAC led to an increase in β-sheet formation in insulin. In contrast, both in the absence and presence of caprate, α-helices, and random structures dominated. These molecular-level insights can guide the design of improved permeability enhancer-based dosage forms, allowing for precise control of peptide release profiles near the intended absorption site.
Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.
Guan C, Li C, Shen X, Yang C, Liu Z, et al. — 2023
INTRODUCTION: Hexarelin exhibits significant protection against organ injury in models of ischemia/reperfusion (I/R)-induced injury (IRI). Nevertheless, the impact of Hexarelin on acute kidney injury (AKI) and its underlying mechanism remains unclear. In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms. METHODS: We assessed the protective effects of Hexarelin through both in vivo and in vitro experiments. In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI. Subsequently, kidney function, histology, and apoptosis were assessed. In vitro, hypoxia/reoxygenation (H/R)-induced HK-2 cell model was used to investigate the impact of Hexarelin on apoptosis in HK-2 cells. Then, we employed molecular docking using a pharmmapper server and autodock software to identify potential target proteins of Hexarelin. RESULTS: In this study, rats subjected to I/R developed severe kidney injury characterized by tubular necrosis, tubular dilatation, increased serum creatinine levels, and cell apoptosis. However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis. This was achieved through the downregulation of conventional apoptosis-related genes, such as Caspase-3, Bax and Bad, and the upregulation of the anti-apoptotic protein Bcl-2. Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells. Furthermore, our analysis using GSEA confirmed the essential role of the apoptosis pathway in I/R-induced AKI. Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin's anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53. To validate these findings, we evaluated the relative expression of MDM2 and p53 in I/R-induced AKI with or without Hexarelin pre-administration and observed a significant suppression of MDM2 and p53 by Hexarelin in both in vivo and in vitro experiments. CONCLUSION: Collectively, Hexarelin was identified as a promising medication in protecting apoptosis against I/R-induced AKI.