Additional Research Compound · For laboratory research use only
Also known as Ibutamoren
MK-677 (ibutamoren mesylate, also L-163,191 and MK-0677) is a non-peptide spiroindoline sulfonamide growth hormone secretagogue developed at Merck. Its design and biological activities were reported in 1995, when it was selected for clinical study1. It acts at the growth hormone secretagogue receptor (GHSR-1a), the G protein-coupled receptor later identified as the receptor for ghrelin3,4.
Published research includes in vitro pituitary cell assays, endocrine studies in dogs and rats, receptor structural biology, rodent neurodegeneration models and registered clinical trials1,2,4,5,6,7.
As described in the research literature
As described in the research literature, MK-677 released growth hormone from rat pituitary cells in culture and was reported to be mechanistically indistinguishable from the growth hormone-releasing peptide GHRP-6, but distinguishable from growth hormone-releasing hormone1. The receptor through which this class of compounds acts was cloned from swine and human pituitary and hypothalamus in 1996 and characterised as a G protein-coupled receptor controlling pulsatile growth hormone release3.
A 2021 cryo-EM study resolved structures of the human ghrelin receptor in complex with Gi and either ghrelin or ibutamoren, and used mutagenesis to map the binding of each agonist4. In beagles, MK-677 raised growth hormone and IGF-I, and cortisol rose more modestly; prolactin and LH were unaltered2. The 1995 report likewise noted modest increases in cortisol in dogs1.
What published studies have examined
Rat pituitary cell assays and endocrine profiling in dogs characterised MK-677 against GHRP-6, the earlier non-peptide secretagogue L-692,429 and growth hormone-releasing hormone1. The secretagogue receptor was cloned and characterised using this class of compounds3, and the structural basis of its activation by ibutamoren has been resolved by cryo-EM4.
Studies in beagles measured growth hormone, IGF-I, cortisol, insulin, glucose, LH, prolactin and thyroxine2. A six-week study in rats examined body growth, tibia length, epiphyseal plate width and IGF-I, and reported that the growth hormone response was lost by six weeks, with increased hypothalamic somatostatin expression5.
In 5XFAD transgenic mice, a model of amyloid-beta accumulation, studies examined amyloid deposition, gliosis, neuronal and synaptic markers in the neocortex and pCREB in the hippocampal dentate gyrus6.
Sources [6]
A 2-year, double-blind, randomised, placebo-controlled, modified-crossover trial in 65 healthy adults aged 60 to 81 used fat-free mass and abdominal visceral fat after 1 year as its primary end points7.
Sources [7]
Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.
Patchett AA, Nargund RP, Tata JR, et al. Proceedings of the National Academy of Sciences of the United States of America, 1995.
MK-0677, a potent, novel, orally active growth hormone (GH) secretagogue: GH, insulin-like growth factor I, and other hormonal responses in beagles.
Jacks T, Smith R, Judith F, et al. Endocrinology, 1996.
A receptor in pituitary and hypothalamus that functions in growth hormone release.
Howard AD, Feighner SD, Cully DF, et al. Science, 1996.
Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren.
Liu H, Sun D, Myasnikov A, et al. Nature Communications, 2021.
Effect of the Orally Active Growth Hormone Secretagogue MK-677 on Somatic Growth in Rats.
Lee J, Kwon A, Chae HW, et al. Yonsei Medical Journal, 2018.
MK-0677, a Ghrelin Agonist, Alleviates Amyloid Beta-Related Pathology in 5XFAD Mice, an Animal Model of Alzheimer's Disease.
Jeong YO, Shin SJ, Park JY, et al. International Journal of Molecular Sciences, 2018.
Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.
Nass R, Pezzoli SS, Oliveri MC, et al. Annals of Internal Medicine, 2008.
PubMed 18981485 ↗DOI 10.7326/0003-4819-149-9-200811040-00003 ↗
This page is provided for research and educational reference only. It does not constitute medical advice, dosing guidance, or a recommendation for use. All compounds are strictly for laboratory and in-vitro research purposes.