Ibutamoren (MK-677)

What Is Ibutamoren?

Ibutamoren is a synthetic small molecule that stimulates growth hormone release by acting on the growth hormone secretagogue receptor, the same receptor activated by the hormone ghrelin. It belongs to the non-peptide growth hormone secretagogues, and a 1997 review called MK-0677 the most interesting molecule among them.^[1]

A 2022 analytical study described ibutamoren as a potent, long-acting, selective non-peptide secretagogue that can be taken orally.^[2] Its non-peptide structure sets it apart from the peptide secretagogues such as GHRP-2, GHRP-6 and hexarelin, which were the starting point for its design.^[3]

Human research on ibutamoren includes small metabolic studies in healthy volunteers, a phase IIb trial in older adults recovering from hip fracture, and preliminary pediatric work. Its growing use as an unregulated performance product has also produced safety case reports and anti-doping studies.^[4][5][6][7]

Chemical Structure and Molecular Identity

Ibutamoren is a non-peptide molecule built on a spiro[indoline-3,4′-piperidine] scaffold bearing a methanesulfonyl group, linked to an O-benzyl-D-serine unit and a 2-amino-2-methylpropanamide side chain. PubChem lists it under CID 178024 with the molecular formula C27H36N4O5S and a molecular weight of 528.7 g/mol.

The IUPAC name is 2-amino-2-methyl-N-[(2R)-1-(1-methylsulfonylspiro[2H-indole-3,4′-piperidine]-1′-yl)-1-oxo-3-phenylmethoxypropan-2-yl]propanamide. The molecule has a single defined stereocenter in the R configuration. Clinical studies have used ibutamoren mesylate, a salt form.^[5]

Key identifiers

• CAS numbers listed in PubChem: 159634-47-6 (free base) and 192511-65-2
• InChIKey: UMUPQWIGCOZEOY-JOCHJYFZSA-N
• Synonyms: MK-677, MK-0677, L-163,191

In thoroughbred horses, liquid chromatography with high-resolution mass spectrometry identified 22 ibutamoren metabolites, 17 phase I and 5 phase II. Oxidation produced mono- and dihydroxylated products, side chains such as the benzyl group and 2-amino-2-methylpropanamide dissociated, and glucuronide conjugates formed, while no sulfonic acid conjugates were observed.^[2]

Research History and Development

Ibutamoren came out of a reverse-pharmacology program that sought orally active small molecules able to restore a youthful growth hormone and IGF-1 profile. When the program began, neither the receptor nor the natural ligand controlling growth hormone pulse amplitude was known, so lead compounds were chosen by function.^[8]

Researchers used the peptide GHRP-6 as a template to discover a series of non-peptide secretagogues, including L-692,429, L-692,585 and MK-0677.^[3] The lead developer reasoned that growth hormone pulses could be amplified by increasing GHRH release, amplifying GHRH signaling in the pituitary, reducing somatostatin release or antagonizing somatostatin signaling, and later reported that the secretagogues act through all four mechanisms.^[8]

The growth hormone secretagogue receptor was then identified by expression cloning as a previously unknown G-protein-coupled receptor found mainly in brain, pituitary and pancreas. Using the cloned receptor, researchers identified ghrelin as its endogenous agonist, and knockout mouse studies confirmed that the secretagogues are ghrelin mimetics.^[8]

Mechanisms Studied in Research

Ibutamoren acts as a ghrelin mimetic at the growth hormone secretagogue receptor, increasing growth hormone secretion and, downstream, circulating IGF-1. Knockout studies of the receptor confirmed this mode of action for the secretagogue class.^[8]

Pathways that raise growth hormone

• Hypothalamic input: secretagogues increase GHRH release and reduce somatostatin release.^[8]
• Pituitary signaling: they amplify GHRH signaling in somatotroph cells and antagonize somatostatin receptor signaling.^[8]
• Dual site of action: GHRP-class compounds probably act on both pituitary and hypothalamus, with activity synergistic with GHRH.^[3]

Downstream effects

In healthy volunteers, ibutamoren produced a large growth hormone peak on the first treatment day (55.9 µg/L versus about 9 µg/L with placebo) and a smaller peak after a week (22.6 µg/L versus about 7 µg/L), consistent with partial attenuation of the acute response.^[4] In older adults after hip fracture, IGF-1 rose by 51.4 ng/mL relative to placebo.^[5] Reported side effects linked to the compound include edema, increased appetite and muscle pain.^[7]

Key Findings From Published Studies

Clinical studies show that ibutamoren reliably raises growth hormone and IGF-1 and can improve nitrogen balance, but functional benefits in older adults were limited and a heart failure safety signal ended its phase IIb hip-fracture trial.

Diet-induced catabolism in healthy adults

In a double-blind, randomized, placebo-controlled crossover study, eight healthy volunteers aged 24 to 39 underwent two 14-day periods of caloric restriction. During the treatment week, mean daily nitrogen balance was +0.31 g/day with ibutamoren versus -1.48 g/day with placebo, and the integrated nitrogen balance response also favored ibutamoren. During the preceding diet-only week, nitrogen losses and the fall in IGF-1 were similar in both groups.^[4]

Older adults in the secretagogue program

The program’s lead developer reported that growth hormone secretagogues reproduced a young adult growth hormone profile in elderly subjects, accompanied by increased bone mineral density and lean mass, modest improvements in strength and improved recovery from hip fracture. Restoration of thymic function was reported in old mice.^[8]

Hip fracture recovery in older adults

A multicenter, randomized, double-blind phase IIb trial enrolled 123 elderly patients recovering from hip fracture. At 24 weeks, gait speed improved relative to placebo, but stair-climbing power did not differ significantly and several other functional measures showed no improvement. Fewer patients in the ibutamoren group fell, though the difference was not significant. The trial was terminated early because of a congestive heart failure safety signal in a limited number of patients, and the authors concluded the compound has an unfavorable safety profile in this population.^[5]

Broader reviews and case reports

• A 2026 scoping review of six peptides used in sports medicine found that 67% of publications used preclinical animal models, that human studies were few and mostly lacked robust controls, and that human data showed modest improvements at best; it associated MK-677 with significant risks including congestive heart failure.^[9]
• A 2025 case report described transaminitis in a healthy man in his early 30s after two months of use, resolving after he stopped.^[7]
• A 2025 pediatric review presented preliminary data on ibutamoren in children with partial growth hormone deficiency.^[6]

Because ibutamoren is often sold outside regulated channels, researchers typically verify identity and purity with HPLC and mass spectrometry certificates of analysis.

Regulatory and Research Status

Ibutamoren is not approved by the US Food and Drug Administration for any medical use and remains an investigational compound. It is prohibited in sport by the World Anti-Doping Agency as a growth hormone secretagogue, and doping-control laboratories have developed methods to detect it.^[2][10]

In horses, the parent compound persisted for up to 72 hours and major metabolites were detectable for up to 96 hours after a single administration.^[2] In human hair, a 2026 study detected ibutamoren after a single exposure and at roughly 170-fold higher concentrations in a performance-enhancing user, the first report of its incorporation into hair, and established a minimal detectable exposure to aid interpretation of anti-doping hair tests.^[10]

A case report noted that ibutamoren is gaining popularity among performance-enhancing supplements, and a sports medicine review observed that such products are often perceived as low risk despite missing efficacy or safety data.^[7][9] Current clinical interest centers on pediatric growth hormone deficiency, where data remain preliminary.^[6]