MK-677
Research OnlyAlso known as: Ibutamoren, Ibutamoren Mesylate, L-163,191, Nutrobal
An orally-active, non-peptide growth hormone secretagogue that mimics ghrelin's effects on GHS-R1a. While not technically a peptide, it is frequently researched alongside peptides for its sustained IGF-1 elevation. Completed Phase 2 trials for muscle wasting, sleep, and bone density. Not FDA approved; WADA prohibited.
Research Statistics
Oral GHS-R1a agonist with 18 human studies across multiple countries and well-characterized ghrelin receptor mechanism; Phase 2 trials completed but regulatory approval abandoned.
Research Dossier
Overview
What is MK-677 and what does the research say?
Mechanism of Action
MK-677 is a non-peptide ghrelin receptor agonist with extensive human clinical trial data. Unlike injectable peptide secretagogues, it offers oral bioavailability and sustained 24-hour effects.
How It Works (Simplified)
MK-677 mimics ghrelin to stimulate growth hormone release through four key pathways:
Binds to ghrelin receptor on pituitary somatotrophs, triggering calcium-mediated GH vesicle release without affecting pulse frequency.
Hepatic IGF-1 synthesis remains elevated for 24+ hours, providing sustained anabolic signaling unlike short-acting peptide secretagogues.
Hypothalamic receptor activation modulates sleep architecture, increasing REM and Stage 4 deep sleep by up to 50%.
~60-65% absorbed through GI tract, surviving stomach acid unlike peptides. Single daily dose maintains effect for 24 hours.
Scientific Pathways
GHS-R1a Signaling Cascade (Growth Hormone Release)
MK-677 (oral) → GI absorption → Systemic circulation
↓
Binds GHS-R1a on pituitary somatotrophs
↓
Gαq/11 → PLC → IP3 + DAG
↓
Intracellular Ca²⁺ release
↓
GH vesicle exocytosisDownstream Anabolic Pathway (IGF-1 Elevation)
Pulsatile GH release → Hepatic GH receptor activation → IGF-1 synthesis
↓
Sustained 24-hour IGF-1 elevation
↓
Protein synthesis / Bone formation / Fat metabolismKey Research: Chapman IM et al. demonstrated dose-dependent GH elevation restoring IGF-1 to young adult levels in elderly subjects. PMID:9771850
Important Limitations
- Not a peptide - Small molecule spiroindoline compound, included due to same receptor target as GHRP-6/Ipamorelin
- Development discontinued after Phase 2 despite positive results - commercial rather than safety reasons
- Increases appetite via ghrelin pathway (may be unwanted)
- Mild glucose/insulin effects require monitoring in pre-diabetic individuals
- WADA prohibited in all sports; detectable via mass spectrometry
Evidence-Chained Benefits
Evidence-Chained Benefits
Research findings linked to mechanisms and clinical outcomes
What to Expect
Timeline based on observations from published studies. Individual responses may vary.
Rapid IGF-1 elevation begins within days of first dose. Human studies show measurable GH increases after single dose. Sleep quality improvements (increased REM and Stage 4 deep sleep) often reported within first week. Increased appetite common due to ghrelin pathway activation.
IGF-1 levels continue to rise toward young adult reference range. Water retention and mild joint fullness may occur. Improved recovery and sleep quality typically noticeable. Appetite stimulation persists.
Steady-state IGF-1 elevation achieved. Body composition changes (increased lean mass, possible fat reduction) may become measurable. Continued sleep architecture improvements. Monitor fasting glucose in susceptible individuals.
Long-term studies (up to 2 years) show sustained IGF-1 elevation and bone mineral density improvements. Body composition benefits continue. Glucose/insulin effects require ongoing monitoring. No tachyphylaxis observed in clinical trials.
Research-Based Observations
This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.
Quality Checklist
Visual indicators to help evaluate MK-677 product quality
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (6 indicators)
For Research Evaluation Only
These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.
Peptide Interactions
Known and theoretical interactions when combining MK-677 with other peptides. Based on published research and mechanistic considerations.
CJC-1295
SynergisticMK-677 (ghrelin mimetic) combined with CJC-1295 (GHRH analog) may produce synergistic GH release through dual pathway activation - similar to GHRP+GHRH synergy.
Sermorelin
SynergisticGHRH analog (sermorelin) plus GHS-R1a agonist (MK-677) may synergistically enhance GH release through complementary signaling pathways.
Tesamorelin
SynergisticSimilar to sermorelin - GHRH+GHS dual pathway activation may amplify GH response compared to either alone.
Ipamorelin
CautionBoth act on GHS-R1a receptor. MK-677's 24-hour action may make additional GHRP peptides redundant. Consider potential receptor saturation.
GHRP-6
CautionBoth are ghrelin receptor agonists. MK-677's sustained action overlaps with GHRP-6's pulsatile effects - combining may be redundant rather than synergistic.
GHRP-2
CautionSimilar mechanism overlap as GHRP-6. MK-677's oral convenience and 24-hour duration often makes it preferred over injectable GHRPs rather than combined.
AOD-9604
CautionMK-677 elevates endogenous GH while AOD-9604 is a non-functional GH fragment. Combining active GH stimulation with failed GH fragment lacks scientific rationale.
Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.
References
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
Methodology Note
This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.
For complete methodology details, see our Methodology page.
Important Disclaimer
This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.
Get Research Alerts
New dossiers and major study summaries delivered to your inbox. Evidence-graded, citation-backed research you can trust.
No spam. Unsubscribe anytime.
Compare MK-677
MK-677 Calculators
Related Peptides
CJC-1295
DAC:GRF, Modified GRF 1-29, Tetrasubstituted GRF
A synthetic analog of growth hormone-releasing hormone (GHRH) with extended half-life. Limited clinical development; not approved for any indication.
Follistatin
FST, FS-344, FS-315 +1 more
An endogenous glycoprotein that inhibits myostatin and activin signaling, potentially allowing muscle growth beyond genetic limits. Gene therapy trials for muscular dystrophy show promise, but injectable peptide forms remain unapproved and understudied in humans.
Human Chorionic Gonadotropin (hCG)
hCG, Choriogonadotropin, Pregnyl +5 more
A glycoprotein hormone FDA-approved for ovulation induction, cryptorchidism, and hypogonadotropic hypogonadism. Functions as an LH receptor agonist with over 50 years of clinical use in reproductive medicine. Gold standard trigger for assisted reproductive technology.
Hexarelin
Examorelin, HEX, Growth Hormone Releasing Hexapeptide +2 more
The most potent synthetic GHRP (Growth Hormone Releasing Peptide), a hexapeptide that strongly stimulates GH release via the ghrelin receptor. Notable for cardioprotective effects independent of GH release. Development discontinued due to rapid desensitization with repeated dosing. Italian research leads global investigation.
HMG
Human Menopausal Gonadotropin, Menotropins, hMG +4 more
A urinary-derived glycoprotein hormone preparation containing both FSH and LH in approximately 1:1 ratio, FDA-approved for female infertility (ovulation induction, ART) and male hypogonadotropic hypogonadism. First used clinically in 1961 by Bruno Lunenfeld, HMG enabled the birth of the first American IVF baby in 1981 and remains a cornerstone of fertility medicine with over 60 years of clinical experience. Highly purified preparations (HP-hMG) demonstrate comparable or slightly superior live birth rates compared to recombinant FSH in IVF.
IGF-1 LR3
Long R3 IGF-1, LR3-IGF-1, Insulin-like Growth Factor 1 Long R3
A modified form of IGF-1 with an extended half-life due to reduced binding protein affinity. Used primarily in research for muscle growth and metabolic effects. Not approved for human use; significant safety concerns exist.
Related Content
GHRP-6
Hormonal · moderate evidence
GHRP-2
Hormonal · moderate evidence
Ipamorelin
Hormonal · moderate evidence
What is MK-677?
An introduction to MK-677, an oral growth hormone secretagog...
AOD-9604 vs MK-677
View side-by-side analysis
CJC-1295 vs MK-677
View side-by-side analysis