MK-677

MK-677, also known as ibutamoren, is a non-peptide, orally active agonist of the ghrelin receptor (GHSR-1a), belonging to the spiroindoline class of small molecules. Unlike most compounds featured on this site, which are peptide chains, MK-677 is structurally distinct as a small molecule with a molecular formula of C₂₇H₃₆N₄O₅S and a molecular weight of 528.67 g/mol. It is identified chemically by CAS numbers 159634-47-6 (free base) and 159752-10-0 (mesylate salt), and can be referenced in PubChem under CID 178024. Originating from Merck’s research pipeline, MK-677 was initially designated under developmental codes MK-0677 and L-163,191.

Functionally, MK-677 acts by activating the ghrelin receptor located in the pituitary and hypothalamus, thereby stimulating pulsatile growth hormone (GH) secretion. This mechanism mimics the body’s endogenous ghrelin/GH-secretagogue signaling pathway, resulting in increased circulating levels of GH and subsequently insulin-like growth factor 1 (IGF-1). Unlike peptide GH secretagogues such as ipamorelin, CJC-1295, GHRP-2, GHRP-6, and hexarelin, which require injection due to their peptide nature, MK-677’s small molecule structure allows for oral administration, offering a distinct pharmacokinetic and pharmacodynamic profile.

The compound’s high affinity for the ghrelin receptor is evidenced by a Ki value of approximately 0.4 nM at GHSR-1a, indicating potent receptor engagement. This oral GH secretagogue activity was demonstrated in a foundational, peer-reviewed study involving healthy elderly subjects aged 64 to 81, where daily oral doses of MK-677 (2, 10, and 25 mg) over 14 and 28 days significantly elevated 24-hour mean GH concentrations by up to 97% and restored serum IGF-1 levels to those typical of younger adults.

Despite its promising pharmacological profile, MK-677’s clinical development was discontinued by Merck after Phase II/III trials in various populations, including Alzheimer’s disease and hip-fracture patients, failed to meet primary efficacy endpoints. Notably, a safety signal emerged during these trials, with an increased incidence of congestive heart failure (CHF) reported in treated subjects compared to placebo, a concern corroborated across the development program. MK-677 has never received FDA approval for any indication.

As of 2026, MK-677 was removed from the FDA’s Category 2 bulk drug substances list and referred back to the Pharmacy Compounding Advisory Committee for further review. This regulatory action pertains solely to compounding pharmacy categorization and does not equate to drug approval status, which remains absent. Currently, MK-677 is available exclusively through research chemical and peptide suppliers for laboratory research purposes only.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

MK-677 (Ibutamoren) is a non-peptide, orally active ghrelin receptor (GHSR-1a) agonist belonging to the spiroindoline class of small molecules, distinct structurally from the peptide chains typical of most compounds in this research category. With a high binding affinity (Ki approximately 0.4 nM) at the ghrelin receptor, MK-677 mimics the endogenous ghrelin and growth hormone secretagogue signaling pathway to stimulate pulsatile growth hormone (GH) release from the pituitary and hypothalamus. This stimulation subsequently elevates circulating insulin-like growth factor 1 (IGF-1) levels. Unlike peptide-based GH secretagogues that require injection, MK-677 is orally bioavailable, offering a mechanistically novel approach to activating the GH-IGF-1 axis.

The foundational peer-reviewed evidence for MK-677’s biological activity derives from Chapman et al.’s 1996 study published in the Journal of Clinical Endocrinology & Metabolism (PMID 8954023). This randomized clinical trial enrolled 32 healthy elderly subjects aged 64 to 81 years and administered oral MK-677 at doses of 2 mg, 10 mg, and 25 mg daily over 14 and 28 days. The highest dose, 25 mg/day, produced a significant 97% increase in mean 24-hour GH concentration and restored serum IGF-1 levels to those typically observed in young adults. These results demonstrate MK-677’s capacity to effectively activate the GH-IGF-1 axis in an aging population, supporting its utility as a potent oral GH secretagogue. The study’s rigorous design and publication in a well-regarded journal make it a key reference for researchers investigating GH modulation through ghrelin receptor agonism.

However, subsequent clinical development revealed important safety concerns and efficacy limitations. A notable safety-signal study by Adunsky et al. (2011), published in Archives of Gerontology and Geriatrics, investigated MK-677 in 123 elderly patients recovering from hip fracture. Subjects received 25 mg/day or placebo for 24 weeks. The trial reported a higher incidence of congestive heart failure (CHF) in the MK-677 group (4 out of 62 patients) compared to placebo (1 out of 61 patients), representing a meaningful safety signal. This finding aligns with a broader MK-677 development program safety profile, where CHF rates were approximately 6.5% in treated subjects versus 1.7% in controls. Such cardiovascular concerns are critical in evaluating the risk-benefit balance of MK-677 and warrant careful consideration in any experimental design or mechanistic study.

Despite its promising endocrine effects, Merck discontinued the clinical development of MK-677 following Phase II and III trials, including studies in Alzheimer’s disease and hip-fracture populations, which failed to meet primary efficacy endpoints. The CHF safety signal compounded these efficacy challenges, contributing to the termination of its regulatory approval pursuit. MK-677 has never received FDA approval for any indication. Furthermore, on April 15, 2026, MK-677 was removed from the FDA’s Category 2 bulk drug substances list and referred back to the Pharmacy Compounding Advisory Committee for review starting July 2026. This regulatory action pertains solely to compounding pharmacy categorization and does not confer drug approval status. MK-677 remains unapproved by the FDA for therapeutic use.

Currently, MK-677 is available exclusively through research chemical channels for laboratory research use. It is intended strictly for experimental applications and is not for human consumption. Researchers can access the primary literature on MK-677 via PubMed and NIH resources to further explore its pharmacology, endocrine effects, and safety profile. The compound’s unique pharmacodynamic properties and mixed clinical outcomes underscore the importance of rigorous preclinical and translational research to elucidate its mechanisms and potential applications.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

MK-677 (Ibutamoren) is uniquely distinguished within the growth hormone secretagogue research field as a non-peptide, orally active agonist of the ghrelin receptor (GHSR-1a). Unlike most compounds in this category, which are peptide chains requiring injection, MK-677 is a spiroindoline-class small molecule with a high affinity for GHSR-1a (Ki ~0.4 nM). This structural distinction has often been overlooked in research discussions, yet it fundamentally sets MK-677 apart by enabling oral bioavailability and ease of administration, a significant pharmacological milestone achieved in the 1990s. At that time, developing an orally active ghrelin mimetic capable of stimulating endogenous pulsatile growth hormone (GH) release was a major advance, as prior GH secretagogues were predominantly peptides necessitating parenteral delivery.

Merck’s extensive clinical development program for MK-677 demonstrated robust pharmacodynamic effects, notably in a foundational study where daily oral doses (2, 10, or 25 mg) over 14 to 28 days in elderly subjects nearly doubled 24-hour GH concentrations and restored IGF-1 levels to those typical of young adults. Despite these promising endocrine outcomes, the compound ultimately failed to meet primary efficacy endpoints in Phase II/III trials targeting conditions such as Alzheimer’s disease and recovery from hip fracture. Compounding this lack of clinical efficacy was a significant safety concern: a reproducible signal of increased congestive heart failure (CHF) incidence in treated populations. For example, one placebo-controlled trial reported CHF rates of 6.5% in the MK-677 group versus 1.7% in controls across the development program, a finding that contributed materially to the discontinuation of further clinical advancement.

Regulatory developments have continued to evolve independently of MK-677’s clinical status. In April 2026, the compound was removed from the FDA’s Category 2 bulk drug substances list, a regulatory classification related to pharmacy compounding rather than drug approval. This action referred MK-677 back to the Pharmacy Compounding Advisory Committee (PCAC) for review starting July 2026, underscoring ongoing regulatory scrutiny distinct from its never-approved drug status. Today, MK-677 remains available solely for laboratory research use through research chemical channels, consistent with Verified Peptides’ commitment to supplying compounds strictly for investigative purposes and not human consumption.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

MK-677 (Ibutamoren) is a non-peptide, orally active small molecule with a distinct spiroindoline structure, necessitating specialized analytical methods for identity and purity verification that differ from those used for peptide chains. At Verified Peptides, we recognize that rigorous quality assurance is critical for research-grade MK-677 to ensure consistent experimental outcomes. Our sourcing protocols mandate comprehensive third-party certification of analysis (COA) from reputable laboratories, confirming the compound’s compliance with stringent purity specifications.

Purity assessment for MK-677 primarily employs high-performance liquid chromatography (HPLC) to quantify the compound’s purity level, typically aiming for ≥98% purity to minimize confounding variables in research applications. Given MK-677’s small-molecule nature, mass spectrometry (MS) is an essential complementary technique used to confirm molecular identity by detecting the precise molecular weight (528.67 g/mol) and verifying the presence of characteristic fragment ions. This orthogonal approach ensures that the supplied MK-677 matches the expected chemical profile, including verification of the molecular formula C27H36N4O5S and the correct salt form, such as the mesylate.

Our sourcing emphasizes traceability and batch-to-batch consistency, with each lot undergoing stringent quality control to detect potential impurities or degradation products that could impact research integrity. Stability testing under recommended storage conditions further supports the maintenance of compound integrity over time. By adhering to these rigorous standards, Verified Peptides provides MK-677 suitable exclusively for laboratory research purposes, supporting scientific investigations into its pharmacodynamic properties without the uncertainties associated with unverified materials.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.

MK-677 (Ibutamoren) is a small-molecule, non-peptide compound typically supplied as a stable powder or in solution form for laboratory research use. Unlike peptide-based compounds, which often require lyophilized storage and strict cold-chain management, MK-677 exhibits greater inherent chemical stability under standard laboratory conditions. However, to maintain optimal potency and integrity, it is recommended to store MK-677 powder in a tightly sealed container, protected from exposure to light and moisture, which can potentially degrade the compound over time. Desiccants and inert atmosphere packaging may further enhance stability by minimizing hydrolytic or oxidative degradation pathways.

Room temperature storage (approximately 20-25°C) is generally acceptable for short to medium-term periods if the compound is kept dry and shielded from direct light. For extended storage durations, refrigeration at 2-8°C is advisable to slow any potential degradation processes, although freezing is not typically necessary. Solutions of MK-677 should be prepared fresh when possible, as prolonged storage in solution form, especially aqueous, can increase the risk of hydrolysis or other chemical changes. Stability can also depend on solvent choice and container material, with amber glass vials recommended to reduce photodegradation risks.

Laboratories should monitor compound integrity using appropriate analytical methods such as HPLC or mass spectrometry when stability over time is critical to experimental outcomes. Overall, MK-677’s small-molecule nature allows for more flexible storage than peptide analogs, but careful handling to avoid moisture and light exposure remains essential for preserving research reliability.

For research purposes only. Not for human consumption. Not FDA approved. Consult a licensed physician.