MK-677
| Category | Compounds |
|---|---|
| Also known as | Ibutamoren, L-163,191, MK-0677 |
| Last updated | 2026-04-14 |
| Reading time | 3 min read |
| Tags | growth-hormone-secretagogueghrelin-agonistoralresearch |
Overview
MK-677, commonly called ibutamoren, is an orally active small-molecule agonist of the growth hormone secretagogue receptor (GHSR-1a), the same receptor activated by ghrelin and by peptide growth hormone secretagogues such as GHRP-2, GHRP-6, Ipamorelin, and Hexarelin. Unlike those peptides, MK-677 was designed for oral bioavailability and sustained action, making it a unique compound within the GH secretagogue class.
Clinical studies initially evaluated MK-677 for conditions of GH deficiency, sarcopenia in older adults, hip-fracture recovery, and cachexia. It produces meaningful increases in pulsatile GH and serum IGF-1 while preserving the physiological pattern of secretion. The program did not proceed to approval, reportedly in part because of effects on glucose tolerance and fluid retention that emerged in certain populations, but MK-677 remained widely available as a research chemical and became popular in fitness communities as a research tool.
MK-677 is frequently cross-referenced with peptide GH secretagogues and with GHRH analogs like Sermorelin, Tesamorelin, CJC-1295, and MOD-GRF(1-29). It is also compared to Macimorelin, another orally active GH secretagogue approved as a diagnostic agent.
Structure / Chemistry
MK-677 is a non-peptide small molecule with a spiropiperidine scaffold (molecular weight ~528 g/mol as the free base). It is resistant to gastrointestinal degradation, which is why it achieves meaningful oral bioavailability that peptide secretagogues generally cannot.
Mechanism of Action
MK-677 agonizes GHSR-1a on somatotrophs in the anterior pituitary and on hypothalamic neurons. Activation triggers calcium-dependent GH release and reduces inhibitory somatostatin tone. The result is elevated pulsatile GH and downstream hepatic IGF-1 production. Ghrelin receptor activation also drives appetite, which is a commonly reported effect.
Research Summary
| Area | Finding | Reference |
|---|---|---|
| Elderly | GH/IGF-1 increases and lean mass gain over 1 year | Nass et al., Ann Intern Med 2008 |
| Obesity | Altered body composition and energy balance | Svensson et al., J Clin Endocrinol Metab 1998 |
| Hip fracture | Mixed functional outcomes in rehab setting | Adunsky et al., Arch Gerontol Geriatr 2011 |
| Pharmacology | Potent, oral GHSR-1a agonist characterization | Smith et al., Science 1993 |
| Growth | GH/IGF-1 elevation in short-stature children | Codner et al., J Pediatr 2001 |
Pharmacokinetics
MK-677 has an oral half-life that supports once-daily dosing, with peak plasma concentrations typically within a couple of hours. Clinical studies most commonly used 10-25 mg daily. Food can blunt peak concentrations. Dosing details reflect trial parameters, not guidance.
Common Discussion Topics
- Effects on insulin sensitivity and fasting glucose.
- Appetite increase from ghrelin receptor agonism.
- Oral convenience vs. injectable peptide secretagogues.
- Preservation of physiological GH pulsatility.
- Research-only status and lack of formal approval.
Related Compounds
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Related entries
- GHRP-2— A synthetic hexapeptide growth hormone secretagogue considered the most potent GHRP by weight, with intermediate selectivity — stronger GH release than GHRP-6 with less appetite stimulation but notable cortisol and prolactin effects.
- GHRP-6— A synthetic hexapeptide growth hormone secretagogue and ghrelin receptor agonist known for potent GH release accompanied by significant appetite stimulation and broader hormonal effects.
- Hexarelin— A synthetic hexapeptide growth hormone secretagogue considered the most potent GHRP for acute GH release, with notable cardiac effects documented in both preclinical and clinical research.
- Ipamorelin— A selective growth hormone secretagogue pentapeptide that stimulates GH release from the pituitary with minimal effects on cortisol, prolactin, and appetite compared to other GHRPs.
- Macimorelin— An orally active synthetic ghrelin receptor agonist approved as a diagnostic agent for adult growth hormone deficiency, representing the first oral growth hormone stimulation test.