Ibutamoren

Ibutamoren (INNTooltip International Nonproprietary Name; developmental code 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 while also raising cortisol levels.^[8]

Ibutamoren

Clinical data
Other names	MK-677; MK-0677; L-163,191; Oratrope
Routes of administration	By mouth
Legal status
Legal status	Investigational New Drug
Pharmacokinetic data
Elimination half-life	4–6 hours (in beagles);[1] IGF-1 levels remain elevated in humans with a single oral dose for up to 24 hours[2]
Identifiers
IUPAC name 2-amino-2-methyl-N-[1-(1-methylsulfonylspiro[2H-indole-3,4'-piperidine]-1'-yl)-1-oxo-3-phenylmethoxypropan-2-yl]propanamide
CAS Number	159634-47-6 Y 159752-10-0 (mesylate)
PubChem CID	9939050
IUPHAR/BPS	5867
DrugBank	DB18214 N
ChemSpider	154975
UNII	GJ0EGN38UL
ChEMBL	ChEMBL13817
CompTox Dashboard (EPA)	DTXSID90166700
ECHA InfoCard	100.236.734
Chemical and physical data
Formula	C27H36N4O5S
Molar mass	528.67 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=S(C)(=O)N(C2)c1ccccc1C23CCN(CC3)C(=O)C(NC(=O)C(N)(C)C)COCc4ccccc4
InChI InChI=1S/C27H36N4O5S/c1-26(2,28)25(33)29-22(18-36-17-20-9-5-4-6-10-20)24(32)30-15-13-27(14-16-30)19-31(37(3,34)35)23-12-8-7-11-21(23)27/h4-12,22H,13-19,28H2,1-3H3,(H,29,33)/t22-/m1/s1 Key:UMUPQWIGCOZEOY-JOCHJYFZSA-N
(verify)

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, ibutamoren dosed at 25 mg/day at bedtime was shown to increase rapid eye movement sleep by 20% and 50% in young and older subjects respectively.^[17] Treatment with ibutamoren also resulted in an approximate 50% increase in slow-wave sleep in young subjects.^[17]

Growth hormone deficiency

In a study of children with growth hormone deficiency, ibutamoren performed better than other growth hormone secretagogues at improving growth hormone levels.^[18] An ongoing study compares ibutamoren directly to injectable hGH in terms of height velocity in this population.^[19] Topline data from Phase 2 OraGrowtH210 and OraGrowtH212 Trials of LUM-201 in PGHD met all primary and secondary endpoints.

Non-research use

Since ibutamoren 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. The use of ibutamoren is banned in most sports.^[20]

See also

• List of growth hormone secretagogues
• Ghrelin