Chemistry:Ibutamoren

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Short description: Experimental drug
Ibutamoren
Ibutamoren skeletal.svg
Clinical data
Other namesMK-677; MK-0677; L-163,191; Oratrope
Routes of
administration		By mouth
Legal status
Legal status
Pharmacokinetic data
Elimination half-life4–6 hours (in beagles);[1] IGF-1 levels remain elevated in humans with a single oral dose for up to 24 hours[2]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC27H36N4O5S
Molar mass528.67 g·mol−1
3D model (JSmol)
  (verify)

Ibutamoren (INN) (developmental code names MK-677, MK-0677, LUM-201, L-163,191; former tentative brand name Oratrope) is a potent, long-acting, orally-active, selective, and non-peptide agonist of the ghrelin receptor and a growth hormone secretagogue, mimicking the growth hormone (GH)-stimulating action of the endogenous hormone ghrelin.[3][4][5][6][7] It has been shown to increase the secretion of several hormones including GH and insulin-like growth factor 1 (IGF-1) and produces sustained increases in the plasma levels of these hormones without affecting cortisol levels.[8]

Effect on lean mass

Ibutamoren has been shown to sustain activation of the GH–IGF-1 axis, increasing growth hormone secretion by up to 97%,[9] and to increase lean body mass with no change in total fat mass or visceral fat. It is under investigation as a potential treatment for reduced levels of these hormones, such as in children or elderly adults with growth hormone deficiency,[3][10][11][12] and human studies have shown it to increase both muscle mass and bone mineral density,[13][14] making it a promising potential therapy for the treatment of frailty in the elderly.[15][16] As of June 2017, ibutamoren is in the preclinical stage of development for growth hormone deficiency.[3]

Effect on sleep architecture

In a small study of 14 subjects, MK-677 dosed at 25mg/day at bedtime was shown to increase REM sleep by 20% and 50% in young and older subjects respectively.[17] Treatment with MK-677 also resulted in an approximate 50% increase in deep sleep in young subjects.[17]

Growth hormone deficiency

In a study of children with growth hormone deficiency, MK-677 performed better than other growth hormone secretagogues at improving growth hormone levels.[18] An ongoing study compares MK-677 directly to injectable hGH in terms of height velocity in this population.[19]

Non-research use

Since MK-677 is still an Investigational New Drug, it has not yet been approved to be marketed for consumption by humans in the United States.[3] However, it has been used experimentally by some in the bodybuilding community. Since it chemically mimics the hormone ghrelin, it functions as a neuropeptide in the central nervous system and crosses the blood-brain-barrier.[4][5][6][7]

See also

  • List of growth hormone secretagogues
  • Ghrelin

References

  1. ↑ Human Growth Hormone: Research and Clinical Practice. Springer Science & Business Media. 28 January 2000. pp. 45–. ISBN 978-1-59259-015-5. https://books.google.com/books?id=Unf5BwAAQBAJ&pg=PA45. 
  2. ↑ "Peptidomimetic regulation of growth hormone secretion". Endocrine Reviews (The Endocrine Society) 18 (5): 621–645. October 1997. doi:10.1210/edrv.18.5.0316. PMID 9331545. 
  3. ↑ 3.0 3.1 3.2 3.3 "Ibutamoren - Lumos Pharma/Merck". AdisInsight. http://adisinsight.springer.com/drugs/800007434. 
  4. ↑ 4.0 4.1 "Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue". Proceedings of the National Academy of Sciences of the United States of America 92 (15): 7001–7005. July 1995. doi:10.1073/pnas.92.15.7001. PMID 7624358. Bibcode: 1995PNAS...92.7001P. 
  5. ↑ 5.0 5.1 "Identification of a new G-protein-linked receptor for growth hormone secretagogues". Molecular Endocrinology 10 (1): 57–61. January 1996. doi:10.1210/mend.10.1.8838145. PMID 8838145. 
  6. ↑ 6.0 6.1 "Identification, characterization, and biological activity of specific receptors for natural (ghrelin) and synthetic growth hormone secretagogues and analogs in human breast carcinomas and cell lines". The Journal of Clinical Endocrinology and Metabolism 86 (4): 1738–1745. April 2001. doi:10.1210/jcem.86.4.7402. PMID 11297611. 
  7. ↑ 7.0 7.1 "Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor". Molecular Pharmacology 75 (1): 44–59. January 2009. doi:10.1124/mol.108.049189. PMID 18923064. 
  8. ↑ "Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men". The Journal of Clinical Endocrinology and Metabolism 81 (8): 2776–2782. August 1996. doi:10.1210/jcem.81.8.8768828. PMID 8768828. 
  9. ↑ Chapman, I. M. (1996). Stimulation of the growth hormone (gh)-insulin-like growth factor I axis by Daily Oral Administration of a GH secretogogue (MK-677) in healthy elderly subjects. Journal of Clinical Endocrinology & Metabolism, 81(12), 4249–4257. https://doi.org/10.1210/jc.81.12.4249
  10. ↑ "Stimulation of the growth hormone (GH)-insulin-like growth factor I axis by daily oral administration of a GH secretogogue (MK-677) in healthy elderly subjects". The Journal of Clinical Endocrinology and Metabolism 81 (12): 4249–4257. December 1996. doi:10.1210/jcem.81.12.8954023. PMID 8954023. 
  11. ↑ "Growth hormone-releasing hormone and growth hormone-releasing peptide as therapeutic agents to enhance growth hormone secretion in disease and aging". Recent Progress in Hormone Research 52: 215–44; discussion 244–6. 1997. PMID 9238854. 
  12. ↑ "Oral administration of growth hormone (GH) releasing peptide-mimetic MK-677 stimulates the GH/insulin-like growth factor-I axis in selected GH-deficient adults". The Journal of Clinical Endocrinology and Metabolism 82 (10): 3455–3463. October 1997. doi:10.1210/jcem.82.10.4297. PMID 9329386. 
  13. ↑ "Oral administration of the growth hormone secretagogue MK-677 increases markers of bone turnover in healthy and functionally impaired elderly adults. The MK-677 Study Group". Journal of Bone and Mineral Research 14 (7): 1182–1188. July 1999. doi:10.1359/jbmr.1999.14.7.1182. PMID 10404019. 
  14. ↑ "Effect of alendronate and MK-677 (a growth hormone secretagogue), individually and in combination, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women". The Journal of Clinical Endocrinology and Metabolism 86 (3): 1116–1125. March 2001. doi:10.1210/jcem.86.3.7294. PMID 11238495. 
  15. ↑ "Ghrelin receptor (GHS-R1A) agonists show potential as interventive agents during aging". Annals of the New York Academy of Sciences 1119 (1): 147–164. November 2007. doi:10.1196/annals.1404.023. PMID 18056963. Bibcode: 2007NYASA1119..147S. 
  16. ↑ "An Anti-frailty Pill For Seniors? New Drug Increases Muscle Mass In Arms And Legs Of Older Adults.". ScienceDaily. 5 November 2008. https://www.sciencedaily.com/releases/2008/11/081104132902.htm. 
  17. ↑ 17.0 17.1 "Prolonged oral treatment with MK-677, a novel growth hormone secretagogue, improves sleep quality in man" (in english). Neuroendocrinology 66 (4): 278–286. October 1997. doi:10.1159/000127249. PMID 9349662. 
  18. ↑ "A GH Secretagogue Receptor Agonist (LUM-201) Elicits Greater GH Responses than Standard GH Secretagogues in Subjects of a Pediatric GH Deficiency Trial". Hormone Research in Paediatrics 95 (1): 76–81. 30 March 2022. doi:10.1159/000524244. PMID 35354138. 
  19. ↑ "Phase 2 Study of LUM-201 in Children With Growth Hormone Deficiency (OraGrowtH210 Trial) - Full Text View - ClinicalTrials.gov" (in en). https://classic.clinicaltrials.gov/ct2/show/NCT04614337. 

External links



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