Name: MK677(Ibutamoren) 100x10mg
Brand: Averlane Labs
Price: 65.00 EUR
Availability: InStock

NOT FOR HUMAN CONSUMPTION

MK677 (ibutamoren) is an oral, non-peptide ghrelin-receptor (GHSR-1a) agonist that provokes pulsatile growth-hormone (GH) release and raises circulating IGF-1. Unlike injectable secretagogues (GHRP-2/hexarelin), MK-677 is once-daily oral, engages central orexigenic circuits (NPY/AgRP), and modestly elevates cortisol and prolactin. It does not activate the androgen receptor and is not a SARM. MK-677 is not FDA/EMA-approved and is prohibited by WADA as a GH-releasing substance.

Additional Benefits of MK-677 Now Under Investigation

Benefit	Key take-aways
1 Lean-mass accrual in older adults	Daily MK-677 increases fat-free mass over months with parallel IGF-1 rises, approximating youthful GH/IGF-1 levels; strength/function show supportive trends when combined with resistance training. <br/><em>Annals of Internal Medicine; JCEM</em>
2 Bone-turnover & BMD signals	Increases bone-formation markers (e.g., P1NP, osteocalcin) and reduces resorption markers; longer-term cohorts report BMD improvements, supporting anti-frailty potential. <br/><em>Bone; Osteoporosis International</em>
3 Sleep architecture	Slow-wave sleep (SWS) and REM density improve with bedtime dosing, aligning with physiologic GH pulses and next-day vitality. <br/><em>Sleep; Psychoneuroendocrinology</em>
4 Appetite & weight in catabolic states	Robust orexigenic effect increases caloric intake; cachexia/rehab pilots show weight and FFM gainswith acceptable tolerability. <br/><em>Clinical Nutrition; Supportive Care in Cancer</em>
5 Glucose handling (mixed)	Some studies show insulin-sensitivity drift (↑ fasting glucose/insulin); others report neutral outcomes with lifestyle control, underscores need for glycaemic monitoring. <br/><em>Diabetes Care; Metabolism</em>
6 Functional recovery after illness/injury	Early programs evaluate MK-677 to speed rehabilitation, leveraging appetite + anabolic endocrine support. <br/><em>Geriatrics & Gerontology International; Archives of Physical Medicine & Rehabilitation</em>
7 GH-axis restoration in age-related decline	Elevates IGF-1/IGFBP-3 toward youthful ranges without exogenous GH injections; preserves pulsatility. <br/><em>Endocrine Reviews; JCEM</em>
8 Quality-of-life domains	Participants frequently report better sleep quality, appetite, and recovery; validated PROs are being incorporated into trials. <br/><em>Endocrine Practice; Quality of Life Research</em>
9 Convenience & adherence	Once-daily oral regimen improves persistence versus injectable GH or peptide secretagogues. <br/><em>Clinical Therapeutics; Patient Preference and Adherence</em>

2. Molecular Mechanism of Action

2.1 Receptor Pharmacodynamics

MK-677 binds GHSR-1a (GPCR) on hypothalamic neurons and pituitary somatotrophs → Gαq/11–PLC–IP₃/Ca²⁺signaling → GH vesicle exocytosis. It synergizes with endogenous GHRH and is partly countered by somatostatin. Central GHSR activation also drives NPY/AgRP orexigenic pathways and modulates sleep circuits.

2.2 Down-stream Biology

Pathway	Functional outcome	Context
GH → GHR–JAK2–STAT5	↑ IGF-1/IGFBP-3, ↑ protein synthesis, lipolysis	Liver, muscle, adipose
GHSR → NPY/AgRP	↑ appetite, ↑ gastric motility	Hypothalamus/GI
Sleep–GH coupling	↑ SWS/REM consolidation, nocturnal GH pulses	CNS
Bone turnover signals	↑ formation markers; BMD over time	Skeleton

3. Pharmacokinetics

Route: Oral (once daily).
Absorption: Rapid; Tmax ~1–2 h.
Half-life: ~4–6 h; IGF-1 elevation persists 24 h with daily dosing due to GH-axis dynamics.
Metabolism: Hepatic; CYP3A4 involvement reported in vitro (DDI potential with strong inhibitors/inducers).
Elimination: Hepatic/renal metabolites; high protein binding.

4. Pre-clinical and Translational Evidence

4.1 Aging/Sarcopenia

Randomized trials in older adults show sustained IGF-1 increases, FFM gains, improved sleep architecture, and favorable trends in strength and gait measures, particularly with structured exercise.

4.2 Bone Health

Markers of bone formation rise within weeks; BMD benefits emerge over longer courses, supporting evaluation for osteopenia/osteoporosis in frailty.

4.3 Metabolism & Diabetes Risk

In mixed-risk cohorts, MK-677 may raise fasting glucose/insulin and reduce insulin sensitivity; effects are dose-, duration-, and phenotype-dependent, emphasizing glycaemic monitoring.

Evidence quality note: Human data include multiple small–moderate RCTs and mechanistic studies; long-term outcomes (fractures, disability, CV events) remain unresolved.

5. Emerging Clinical Interests

Field	Rationale	Current status
Sarcopenia/frailty	Oral anabolic + sleep and appetite support	Phase 2–style signals; larger RCTs needed
Osteopenia/osteoporosis	Bone-turnover and BMD improvements	Exploratory
Cachexia (cancer/COPD/CHF)	Orexigenic + GH/IGF-1 anabolism	Pilot/feasibility
Post-acute rehab	Appetite/FFM restoration to aid recovery	Early translational
Sleep disorders (SWS decline)	SWS augmentation with endocrine coupling	Proof-of-concept

6. Safety and Tolerability

Common: Increased appetite/weight, peripheral edema, transient paresthesias/carpal-tunnel-like symptoms, fatigue, vivid dreams.
Endocrine: IGF-1 elevation (target age-normal range); prolactin and cortisol may rise modestly.
Metabolic: FPG/HbA1c can drift upward; monitor in prediabetes/diabetes and adjust therapy as needed.
CV/Renal: Edema and mild BP increases can occur, use caution in HF/CKD.
GI: Nausea/GERD in a minority.
Neuropsych: Rare insomnia/irritability.
Drug interactions: Caution with strong CYP3A4 inhibitors/inducers (theoretical/limited clinical data).
Contraindications/Caution: Active malignancy under evaluation (IGF-1 biology), pregnancy, uncontrolled diabetes, decompensated HF.

Comparative safety matrix

Concern	MK-677 (oral GHSR agonist)	GHRP-2/Hexarelin (injectable)	Sermorelin/CJC (GHRH analogs)	Somatropin (GH)
Route/frequency	Oral, once daily	SC/IN multiple daily	SC nightly / weekly-biweekly (DAC)	SC/IM daily–weekly
IGF-1 profile	Sustained, higher	Pulsatile, moderate	Physiologic pulses	Dose-driven, sustained
Appetite	↑↑ (orexigenic)	↑ (variable)	Neutral	Neutral
Edema/CTS	Moderate	Mild–moderate	Low–moderate	Moderate
Glycaemic drift	Common (mild–mod.)	Mild	Neutral–mild ↑	Neutral–mild ↑
Prolactin/cortisol	Modest ↑	Transient ↑	Minimal	Minimal

7. Regulatory Landscape

Approvals: None for any indication in major markets.
Sport: WADA-prohibited (S2: growth-hormone releasing substances).
Supply: Often sold as a research chemical; purity/adulteration issues are common outside GMP trials.

8. Future Directions

Large, outcome-focused RCTs in sarcopenia/frailty with function and fall/fracture endpoints.
Bone programs powered for BMD and fracture outcomes.
Metabolic risk management (pre-specified glycaemic thresholds, CGM, cardiometabolic composites).
Dosing/time-of-day studies to optimize sleep/SWS and minimize glycaemic drift.
Combination strategies: Pair with resistance exercise, protein optimization, or incretin-based therapies to balance orexigeny with metabolic safety.
DDI characterization for CYP3A4 interactions and special-population PK.

Selected References

Annals of Internal Medicine; Journal of Clinical Endocrinology & Metabolism, MK-677 increases IGF-1 and fat-free mass in older adults.
Sleep; Psychoneuroendocrinology, Improvements in slow-wave sleep and nocturnal GH coupling.
Bone; Osteoporosis International, Bone-turnover markers and BMD trends under ghrelin mimetics.
Diabetes Care; Metabolism, Glycaemic effects and insulin-sensitivity considerations.
Clinical Pharmacology & Therapeutics, Oral PK/PD characteristics of ghrelin-receptor agonists.
Supportive Care in Cancer; Clinical Nutrition, Appetite/weight and functional recovery in catabolic states.
Endocrine Reviews, Physiology of GH pulsatility and ghrelin signaling.
Drug Testing & Analysis; WADA Prohibited List, Anti-doping status and detection.

MK677(Ibutamoren) 100x10mg

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