Ibutamoren mesylate
[CAS# 159752-10-0]

Identification

• Classification: API >> Hormone and endocrine-regulating drugs >> Pituitary hormone
• Name: Ibutamoren mesylate
• Synonyms: MK-677; 2-Amino-N-[(1R)-2-[1,2-dihydro-1-(methylsulfonyl)spiro[3H-indole-3,4'-piperidin]-1'-yl]-2-oxo-1-[(phenylmethoxy)methyl]ethyl]-2-methylpropanamide methanesulfonate
• Molecular Formula: C₂₇H₃₆N₄O₅S.CH₄O₃S
• Molecular Weight: 624.77
• CAS Registry Number: 159752-10-0
• SMILES: CC(C)(C(=O)N[C@H](COCC1=CC=CC=C1)C(=O)N2CCC3(CC2)CN(C4=CC=CC=C34)S(=O)(=O)C)N.CS(=O)(=O)O

Properties

• Solubility: DMSO 12 mg/mL, Water $lessThan$1 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

Ibutamoren mesylate is a synthetic compound developed in the 1990s during research into growth hormone secretagogues, a class of molecules designed to stimulate the body’s natural production of growth hormone. It is the mesylate salt form of ibutamoren, which is also known by the research code MK-677. The discovery of ibutamoren was part of a larger pharmaceutical effort to find small-molecule alternatives to peptide-based growth hormone releasing agents, with the goal of developing an orally active drug that could mimic the effects of the natural ligand ghrelin. Ghrelin, identified in 1999 as a peptide hormone that binds to the growth hormone secretagogue receptor (GHSR), regulates appetite and growth hormone release. Prior to this discovery, ibutamoren had already been identified as a potent agonist of the same receptor, and its mesylate form was developed to improve stability, handling, and formulation.

The main application of ibutamoren mesylate has been in clinical research related to disorders involving growth hormone deficiency and muscle wasting. By binding to the GHSR, it stimulates the secretion of growth hormone and subsequently increases circulating levels of insulin-like growth factor 1 (IGF-1). Both of these hormones play crucial roles in growth, metabolism, and tissue repair. Clinical studies have demonstrated that ibutamoren mesylate can increase growth hormone and IGF-1 levels in both young and elderly subjects, leading to interest in its potential use for treating growth hormone deficiencies, frailty in older populations, and conditions such as osteoporosis.

Another area of research application has been in the treatment of muscle wasting and cachexia, which are common in chronic illnesses such as cancer and HIV/AIDS. The ability of ibutamoren mesylate to stimulate appetite through ghrelin receptor activation has been of particular interest in this context, since loss of appetite contributes significantly to weight loss in such conditions. Its oral bioavailability distinguishes it from peptide-based therapies, which typically require injection, making it more convenient for long-term administration in clinical settings.

In addition to its applications in endocrinology and metabolic research, ibutamoren mesylate has also been studied in the context of sleep and cognitive function. Activation of the ghrelin receptor has been linked to improvements in sleep quality and architecture, and preliminary studies suggested possible benefits in cognitive performance through indirect mechanisms involving growth hormone and IGF-1. These findings contributed to broader investigations into its potential as a therapeutic tool beyond growth disorders.

Despite the promising results from early studies, ibutamoren mesylate has not been approved for clinical use by regulatory agencies. Research has continued in the form of clinical trials, but its development as a marketed drug has remained limited. Concerns about long-term safety, particularly regarding insulin sensitivity and other metabolic effects, have influenced the pace of its progress. Nonetheless, the compound remains a widely studied example of a non-peptidic, orally active growth hormone secretagogue, and its discovery represented a significant milestone in the search for practical growth hormone modulators.

References

2018. MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer’s Disease. International Journal of Molecular Sciences, 19(6).
DOI: 10.3390/ijms19061800

2011. MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: A multicenter, randomized, placebo-controlled phase IIb study. Archives of Gerontology and Geriatrics, 53(2).
DOI: 10.1016/j.archger.2010.10.004

2008. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial. Annals of Internal Medicine, 149(9).
DOI: 10.7326/0003-4819-149-9-200811040-00003