Growth hormone releasing peptide
[CAS# 87616-84-0]

Identification

• Classification: Biochemical >> Peptide
• Name: Growth hormone releasing peptide
• Synonyms: GHRP-6; (2S)-6-amino-2-[[2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-amino-3-(3H-imidazol-4-yl)propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]propanoyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-3-phenyl-propanoyl]amino]hexanamide
• Molecular Formula: C₄₆H₅₆N₁₂O₆
• Molecular Weight: 873.01
• Protein Sequence: HWAWFK
• CAS Registry Number: 87616-84-0
• SMILES: C[C@@H](C(=O)N[C@@H](CC1=CNC2=CC=CC=C21)C(=O)N[C@H](CC3=CC=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N)NC(=O)[C@@H](CC4=CNC5=CC=CC=C54)NC(=O)[C@H](CC6=CN=CN6)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 1407.0±65.0 °C 760 mmHg (Calc.)^*
• Flash point: 804.7±34.3 °C (Calc.)^*
• Index of refraction: 1.664 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H317-H319
• Safety Statements: P280-P305+P351+P338

Discovery and Applications

Growth hormone releasing peptides (GHRPs) are a class of synthetic peptides that stimulate the release of growth hormone (GH) from the anterior pituitary gland. The discovery of these peptides traces back to the late 1980s and early 1990s when researchers sought alternatives to growth hormone-releasing hormone (GHRH) for therapeutic and research purposes. GHRPs were identified through screening of small synthetic peptides for their ability to enhance GH secretion independently of GHRH. The first reported GHRPs included hexapeptides such as GHRP-6, which demonstrated potent GH-releasing activity and laid the foundation for the development of subsequent analogs.

Structurally, GHRPs are typically short sequences of amino acids, often hexapeptides, designed to mimic or potentiate the action of endogenous ligands at the GH secretagogue receptor (GHS-R1a), a G protein-coupled receptor identified as the target of these peptides. These synthetic peptides were optimized through systematic modifications to improve stability, receptor affinity, and bioavailability. Unlike endogenous GHRH, GHRPs can act independently of the hypothalamic regulation of GH secretion and can synergistically increase GH levels when administered in combination with GHRH.

The primary application of GHRPs is in the stimulation of GH release for clinical and research purposes. In medicine, they have been investigated for the treatment of GH deficiency, age-related decline in GH levels, and conditions associated with catabolism, such as cachexia. By promoting endogenous GH secretion, GHRPs can potentially improve lean body mass, bone density, and metabolic profiles without the need for exogenous GH administration. Their mechanism of action involves binding to the GHS-R1a receptor on pituitary somatotrophs and stimulating intracellular signaling pathways that lead to the synthesis and release of GH.

Beyond clinical applications, GHRPs are widely used in biomedical research to study GH regulation, pituitary function, and the downstream effects of increased GH levels on metabolism and tissue growth. Their relatively short half-lives and well-characterized pharmacodynamics make them useful tools for in vitro and in vivo studies, enabling the controlled investigation of GH-dependent processes. GHRPs have also been utilized as templates for the design of long-acting GH secretagogues and for exploring peptide modifications that enhance receptor selectivity and pharmacological potency.

GHRPs illustrate the translation of peptide chemistry into therapeutics, highlighting how short synthetic sequences can modulate endocrine pathways effectively. Their discovery and application demonstrate the utility of peptide-based strategies in regulating hormone secretion and in developing interventions for endocrine disorders. Today, GHRPs continue to be explored in preclinical and clinical settings, with ongoing research focused on optimizing their efficacy, stability, and safety for potential therapeutic use.

References

2023. Inhibition of ghrelin activity by the receptor antagonist [D-Lys3]-GHRP-6 enhances hepatic fatty acid oxidation and gluconeogenesis in a growing pig model. Peptides, 166.
DOI: 10.1016/j.peptides.2023.171041

2021. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Nature Communications, 12(1).
DOI: 10.1038/s41467-021-25364-2

2020. miR-709 inhibits GHRP6 induced GH synthesis by targeting PRKCA in pituitary. Molecular and Cellular Endocrinology, 506.
DOI: 10.1016/j.mce.2020.110763