What is MK-677?
MK-677 (MK-677 / Ibutamoren Mesylate) is classified as a growth hormone secretagogue / ghrelin receptor agonist (non-peptide). With a molecular weight of 528.66 Da and formula C27H36N4O5S, it is one of the most studied compounds in its class.
This encyclopedia entry covers the molecular profile, mechanism of action, research history, key published studies, and research applications of MK-677. It is part of the Peptides Pharma Peptide Encyclopedia, a scientific reference for researchers working with peptide compounds.
Molecular Profile
MOLECULAR FORMULA
C27H36N4O5S
MOLECULAR WEIGHT
528.66 Da
CLASSIFICATION
Growth Hormone Secretagogue / Ghrelin Receptor Agonist (Non-Peptide)
AMINO ACID SEQUENCE / STRUCTURE
Non-peptide small molecule (spiroindoline sulfonamide scaffold)
Mechanism of Action
MK-677 (Ibutamoren) is a non-peptide, orally active agonist of the growth hormone secretagogue receptor (GHS-R1a), the same ghrelin receptor targeted by peptide secretagogues like GHRP-6 and Ipamorelin. However, unlike those peptides, MK-677 is a small molecule with full oral bioavailability, eliminating the need for injection.
Upon binding to GHS-R1a on pituitary somatotroph cells, MK-677 triggers growth hormone (GH) release in a pulsatile fashion that mimics physiological secretion patterns. It increases both the amplitude and frequency of GH pulses without disrupting the normal circadian rhythm of GH release. This leads to sustained elevation of circulating GH and, consequently, insulin-like growth factor-1 (IGF-1) levels.
MK-677 also has a distinctive mechanism regarding cortisol: while it causes a transient, modest increase in cortisol following initial dosing, this effect does not persist with continued administration. Its long half-life of approximately 24 hours allows once-daily oral dosing, and unlike exogenous GH administration, MK-677 preserves the negative feedback mechanisms that prevent excessive GH accumulation.
Research History
MK-677 was developed by Merck & Co. in the 1990s as part of a programme to create orally available growth hormone secretagogues. The compound was designed through structure-activity relationship studies to mimic ghrelin's action at GHS-R1a while maintaining drug-like oral bioavailability — a significant pharmaceutical achievement.
Clinical trials in the late 1990s and 2000s demonstrated MK-677's ability to increase GH and IGF-1 levels in young and elderly subjects, improve nitrogen balance (an indicator of protein anabolism), enhance sleep quality, and increase bone mineral density over extended treatment periods. A notable 2-year study in elderly adults showed sustained IGF-1 elevation and increased bone mineral density at the femoral neck. Despite promising results, Merck did not pursue FDA approval, and MK-677 remains an investigational compound widely studied in research settings.
Key Published Studies
MK-677, an orally active growth hormone secretagogue, reverses diet-induced catabolism
1998
Demonstrated that MK-677 reversed nitrogen wasting in calorie-restricted subjects, suggesting potent anti-catabolic and anabolic properties mediated by increased GH/IGF-1.
Two-year effects of MK-677 on bone mineral density in elderly adults
2001
Showed that 2 years of daily MK-677 increased bone mineral density at the femoral neck in postmenopausal women, with sustained IGF-1 elevation throughout the study.
Effects of MK-677 on sleep quality and nocturnal GH release
1997
Demonstrated a 50% increase in stage IV (deep) sleep duration and a 20% increase in REM sleep, with enhanced nocturnal GH pulse amplitude in both young and elderly subjects.
Oral administration of growth hormone secretagogue MK-677 increases IGF-1 in elderly subjects
2008
Confirmed sustained IGF-1 elevation to youthful levels in subjects aged 60-81 with daily oral MK-677, without significant changes in cortisol or thyroid hormones.
Research Applications
Growth hormone secretion and IGF-1 research
Body composition and muscle mass studies
Bone density and osteoporosis research
Sleep architecture and quality studies
Age-related GH decline and sarcopenia
Nitrogen balance and anti-catabolic research
Oral GH secretagogue pharmacology