Molecule guides
What Is Ibutamoren (MK-677)? Non-Peptide Ghrelin-Receptor Agonist: Structure, Mechanism, Evidence
MK-677 is a small molecule, not a peptide: orally active, active for about 24 hours, and the source of both its research appeal and its interpretive difficulties.
Key facts
- CAS number: 159752-10-0
- Molecular formula: C27H36N4O5S
- Molecular weight: 528.66 g/mol
- Purity: ≥98% by HPLC; lot-matched COA available
- Form: Oral capsules in a sealed bottle with desiccant
- Storage: Room temperature in the sealed bottle, protected from light, heat and humidity
- Available sizes: 12.5 mg · 30 capsules · 25 mg · 30 capsules
Despite sitting in a peptide catalogue, ibutamoren (MK-677, also MK-0677) is not a peptide at all. It is a small molecule of 528.66 g/mol built on a spiropiperidine scaffold, and it activates GHS-R1a — the same receptor targeted by the growth hormone releasing peptides. Two properties distinguish it from every injectable secretagogue we list. It is orally active, since a compact synthetic molecule survives digestion and first-pass metabolism where a pentapeptide would not. And its reported half-life is about 24 hours, versus minutes for the peptide secretagogues. These two facts explain both why researchers find it attractive and why its data are harder to interpret.
We supply Ibutamoren (MK-677) Capsules as bottles of 30, in 12.5 mg and 25 mg strengths, listed under GHRPs and secretagogues and in the oral capsules format.
Ibutamoren (MK-677) defined
As a growth hormone secretagogue, ibutamoren makes the pituitary release endogenous growth hormone instead of providing the hormone itself. The GHRPs reproduce a peptide pharmacophore; ibutamoren is a peptidomimetic — a small molecule arrived at by structure-guided optimisation that occupies the same binding pocket while looking nothing like ghrelin or the GHRPs chemically.
Identifiers: CAS 159752-10-0, formula C27H36N4O5S, molecular weight 528.66 g/mol; alternative codes MK-0677 and L-163,191. It is normally sold as the mesylate salt. As a small molecule it is stable as a solid at room temperature, is never reconstituted and does not need cold-chain shipping — practically very different from the rest of this product family.
Discovery and structure
The compound came out of Merck's mid-1990s secretagogue programme, whose goal was to turn the pharmacology of peptide GHRPs into an oral drug candidate. The chemistry centred on a spiropiperidine core decorated with sulfonamide and indoline groups, and the lead that emerged combined high receptor affinity, oral absorption and a duration suitable for once-a-day administration. Compounds from this series were used as probes to clone the receptor in 1996, and ghrelin — the endogenous ligand — was only discovered in 1999. In other words, the synthetic mimic existed before the natural hormone it mimics was known, which rarely happens in pharmacology.
Mechanism of action
At the molecular level, ibutamoren is a GHS-R1a agonist. This Gq-coupled receptor is expressed on somatotrophs in the pituitary and in the arcuate nucleus of the hypothalamus. Binding activates phospholipase C, produces IP3 and raises cytosolic calcium, which in pituitary preparations goes hand in hand with the release of secretory granules. The same receptor also transmits ghrelin's appetite signal, so both animal and human studies see increased food intake — a direct consequence of hitting that receptor, not a side observation.
For study design, the pharmacokinetics are the most consequential feature. Natural growth hormone secretion is pulsatile, and peptide secretagogues generate brief pulses that largely preserve that rhythm. A compound lasting 24 hours instead produces almost continuous receptor occupancy. Published data indicate that ibutamoren increases pulse amplitude and 24-hour output while keeping pulsatility intact, yet continuous GHS-R1a occupancy still raises the prospect of receptor desensitisation, which any reading of long-term data must confront.
It is not fully selective. In human studies, cortisol and prolactin rose slightly alongside growth hormone — less than with the older GHRPs, but not the complete absence reported for ipamorelin.
Research applications
Long-term studies in older adults
The human study cited most often is a 2008 randomised, placebo-controlled trial that ran for two years in healthy older adults. It reported sustained rises in growth hormone and IGF-1 with an increase in fat-free mass — and, alongside those, higher fasting glucose, signs of insulin resistance and increased hunger. It is still the best single source on what long-term GHS-R1a agonism does in humans.
Metabolic and glycaemic findings
The glucose finding recurs throughout the literature rather than standing alone. Growth hormone is counter-regulatory, so sustained elevation would be expected to lower insulin sensitivity, and studies in older and obese populations reported effects in the same direction. This is both the main reason the compound interests metabolic researchers and the main reason its development stopped.
Bone, muscle and recovery studies
Other trials looked at markers of bone mineral density and at functional recovery after hip fracture, and separate studies measured nitrogen balance under calorie restriction. Results were mixed: biochemical endpoints moved more consistently than functional ones.
Sleep architecture
Growth hormone secretion is linked to slow-wave sleep, so several studies used polysomnography, reporting changes in slow-wave and REM parameters in both younger and older volunteers.
Development status
Although a considerable body of clinical data exists, ibutamoren never won approval for any indication, and development was dropped. The fair description is an investigational compound with well-documented human pharmacology — neither an unexplored research chemical nor an authorised medicine.
Available formats
Because it comes as a capsule presentation, there is no reconstitution step and no cold chain — the two variables that dominate the handling of freeze-dried peptides. That is why oral small molecules are attractive when preparation error is a concern in a study design. Our guide to oral peptides, capsules and troches covers the broader pros and cons of oral formats.
Handling and storage at the bench
No reconstitution is involved: this is a finished capsule product, not a freeze-dried powder. Store the bottle closed at room temperature with its desiccant, protected from light, heat and damp. Humidity is the real risk — once the desiccant is exhausted or the bottle is left open, gelatin capsules soften and stick together, and fused capsules make accurate quantification difficult, not merely look untidy.
For an in-vitro assay, capsules are the wrong starting material: you need the pure compound, because capsule fillers will disturb a cell-based readout. Ibutamoren has low water solubility and is typically dissolved in DMSO for cell work, then diluted so that the final DMSO concentration stays within the tolerance of the cell line. General storage guidance is in how to store peptides.
Purity and reading the certificate of analysis
A small-molecule certificate reads differently from a peptide one. HPLC purity remains the main number, but identity comes from a mass spectrometry result consistent with 528.66 g/mol — and for a compound of this size, an NMR spectrum is much more conclusive than mass alone, since it can distinguish isomers with an identical formula. The salt form must be declared, because mesylate and free base differ in molecular weight and therefore in how much active compound a nominal 25 mg capsule really holds. For capsules above all, content uniformity is the critical specification: the stated strength has to hold for each capsule in the bottle, not only on average. Our guide to reading a certificate of analysis explains the general layout.
Regulatory position
Ibutamoren has no marketing authorisation as a medicine in any country. Its clinical development ended without approval, so there is no reference product or approved label. It is also not a food supplement: US regulators have concluded it does not qualify as a dietary ingredient. The WADA prohibited list names ibutamoren specifically among growth hormone secretagogues, banned at all times, in and out of competition. What we supply is for laboratory research only, not for human consumption.
Related compounds and further reading
Injectable compounds acting at the same receptor include Ipamorelin, the selective pentapeptide, and secretagogue-plus-GHRH blends such as CJC-1295 + Ipamorelin. If your study needs a peptide comparator instead of the oral small molecule, begin with our ipamorelin explainer; for the bigger picture, see the muscle growth research overview.
Matching catalogue section: GHRPs & Secretagogues
Questions
Is Ibutamoren a peptide?
No. It is a small, non-peptide molecule with a spiropiperidine core (528.66 g/mol) that switches on the receptor used by the growth hormone releasing peptides. Chemically it bears no resemblance to ghrelin or the GHRPs — which is exactly what lets it be taken orally and stored at room temperature.
Which receptor does MK-677 activate?
GHS-R1a, the receptor for ghrelin: a Gq-coupled GPCR located on pituitary somatotrophs and in the arcuate nucleus of the hypothalamus. Its activation drives phospholipase C signalling and a rise in cytosolic calcium. Because this receptor also relays ghrelin's hunger signal, the extra food intake seen in animals and trial participants is an expected on-target effect.
Why is the 24-hour half-life important for experimental design?
Growth hormone is normally released in pulses, and short-lived peptide secretagogues produce brief peaks that broadly respect that pattern. A compound with a 24-hour half-life, by contrast, keeps the receptor occupied almost constantly. Published data indicate that pulsatility is preserved, yet constant GHS-R1a occupancy raises the question of desensitisation, which any interpretation of long-term data must deal with.
What did the two-year human trial find?
A randomised, placebo-controlled study in healthy older adults found lasting increases in growth hormone, IGF-1 and fat-free mass, accompanied by raised fasting glucose, signs of insulin resistance and stronger appetite. No other published study tells us as much about prolonged GHS-R1a agonism.
Has MK-677 ever been approved?
No. Even with a large clinical dataset behind it, no indication was ever approved and development stopped. Nor is it a food supplement — US regulators have found it does not meet the definition of a dietary ingredient — and WADA lists it by name as prohibited.
How should Ibutamoren be stored?
Keep the bottle closed at room temperature with the desiccant inside, away from light, heat and damp. It needs neither reconstitution nor refrigerated transport. The practical risk is moisture: when the desiccant is used up, gelatin capsules soften and fuse, making accurate quantification difficult.
Are capsules suitable for in-vitro experiments?
Not directly. Capsule excipients disturb cell-based readouts, so use the pure compound instead. Because ibutamoren dissolves poorly in water, it is usually taken up in DMSO for cell work and diluted until the final solvent level is one the cells tolerate.