MK-677 (Ibutamoren)

MK-677 (CAS 159752-10-0, alternative names ibutamoren or L-163,191) is a non-peptide growth hormone secretagogue, developed by Merck in the 1990s as an orally bioavailable peptide-mimetic of GHRPs. Despite its spirolactam (non-peptide) structure, it acts on the same target as GHRPs: the GHS-R1a (ghrelin) receptor, with Ki ~1-2 nM affinity and high selectivity.

Key property: oral bioavailability. Unlike peptide GHRPs (GHRP-2, GHRP-6, ipamorelin, hexarelin) requiring injectable administration (subcutaneous or intramuscular) due to gastric degradation, MK-677 exhibits ≥60% oral bioavailability and 4-6 hour plasma half-life. This makes it a major tool for long-term GH stimulation studies with a single daily oral dose.

Mechanism of action. GHS-R1a agonist → Gαq coupling → PLC → IP3/DAG → intracellular Ca²⁺ in pituitary somatotropes → release of stored GH. MK-677 also elevates circulating IGF-1 by 40-70%, IGFBP-3 and restores amplified but preserved GH pulsatility (unlike DAC-equipped CJC-1295). It moderately increases cortisol and prolactin (minor effects vs GHRP-2/6).

Clinical and research data. MK-677 has undergone multiple human clinical trials: Murphy 1998 (adult somatotropic deficiency), Nass 2008 JCEM (elderly subject, body composition effects, 25 mg/d × 12 months restoring IGF-1 to young adult level), Adunsky 2011 (hip fracture, functional recovery acceleration). It is also studied for cachexia, sarcopenia and anorexia. Not approved for human use outside trials. Classified RUO in Europe and USA, banned by WADA (section S2). MK-677 is not part of the Lab Peptides France catalogue; for the GHS-R1a pathway, the catalogue offers ipamorelin, GHRP-2, GHRP-6 and hexarelin.