Explore studies of mk 677.
MK-0677 was characterized as the most potent orally active GH secretagogue, with EC50 of 1.3 nM in vitro, oral efficacy in dogs at 0.125 mg/kg, and confirmed anabolic effects in rodents.
Patchett, A A; Nargund, R P; Tata, J R; Chen, M H; Barakat, K J; Johnston, D B; Cheng, K; Chan, W W; Butler, B; Hickey, G · Animal Study
Daily oral MK-677 significantly stimulated the GH-IGF-1 axis in healthy elderly adults aged 64-81, raising levels toward those seen in younger individuals.
Chapman, I M; Bach, M A; Van Cauter, E; Farmer, M; Krupa, D; Taylor, A M; Schilling, L M; Cole, K Y; Skiles, E H; Pezzoli, S S; Hartman, M L; Veldhuis, J D; Gormley, G J; Thorner, M O · RCT
Bedtime MK-677 at 25 mg for 7 days significantly increased 24-hour GH profiles and IGF-1 in young men without altering adrenocortical function.
Copinschi, G; Van Onderbergen, A; L'Hermite-Balériaux, M; Mendel, C M; Caufriez, A; Leproult, R; Bolognese, J A; De Smet, M; Thorner, M O; Van Cauter, E · RCT
The GH secretagogue receptor was solubilized as a ~255 kDa receptor-ligand-G-protein complex from porcine pituitary, confirming it is distinct from the GHRH receptor.
Pomés, A; Pong, S S; Schaeffer, J M · In Vitro
A specific high-affinity G-protein-linked receptor for GH secretagogues was identified, operating through a distinct signaling pathway from GHRH.
Pong, S S; Chaung, L Y; Dean, D C; Nargund, R P; Patchett, A A; Smith, R G · In Vitro
GH secretagogues act through a novel receptor at dual sites (hypothalamus and pituitary) to amplify natural pulsatile GH release rather than creating continuous artificial elevation.
Smith, R G; Pong, S S; Hickey, G; Jacks, T; Cheng, K; Leonard, R; Cohen, C J; Arena, J P; Chang, C H; Drisko, J; Wyvratt, M; Fisher, M; Nargund, R; Patchett, A · Review
Oral MK-677 stimulated GH and IGF-I in selected severely GH-deficient adults, with responses dependent on residual pituitary secretory capacity.
Chapman, I M; Pescovitz, O H; Murphy, G; Treep, T; Cerchio, K A; Krupa, D; Gertz, B; Polvino, W J; Skiles, E H; Pezzoli, S S; Thorner, M O · RCT
Prolonged oral MK-677 significantly improved sleep quality by increasing stage 4 (deep sleep) and REM sleep in both young (18-30) and older (65+) adults.
Copinschi, G; Leproult, R; Van Onderbergen, A; Caufriez, A; Cole, K Y; Schilling, L M; Mendel, C M; De Lepeleire, I; Bolognese, J A; Van Cauter, E · RCT
GHRH and GHRPs can restore GH secretion in aging and disease, addressing the visceral fat accumulation and metabolic changes associated with GH decline.
Thorner, M O; Chapman, I M; Gaylinn, B D; Pezzoli, S S; Hartman, M L · Review
MK-0677 induced c-Fos expression in arcuate nucleus neurons in vivo, confirming direct hypothalamic activation as a mechanism for its GH-releasing effect.
Bailey, A R; Smith, R G; Leng, G · Animal Study
GH secretagogues function as somatostatin antagonists at the hypothalamic-pituitary level and can restore youthful GH secretion patterns in elderly subjects.
Fuh, V L; Bach, M A · Review
Oral GH secretagogues effectively increase GH and IGF-1 through a specific receptor, with clinical potential spanning GH deficiency, aging, and catabolic states, though their optimal therapeutic role remained to be defined.
Ghigo, E; Arvat, E; Camanni, F · Review
MK-677 at 25 mg daily reversed diet-induced nitrogen wasting in healthy volunteers, increasing IGF-1 by 40% and producing sustained anabolic effects comparable to GH injections.
Murphy, M G; Plunkett, L M; Gertz, B J; He, W; Wittreich, J; Polvino, W M; Clemmons, D R · RCT
MK-677 (25 mg/day for 8 weeks) increased bone formation markers more than resorption markers in 24 obese young males, with elevated IGF-1 levels suggesting a growth hormone-mediated anabolic bone effect.
Svensson, J; Ohlsson, C; Jansson, J O; Murphy, G; Wyss, D; Krupa, D; Cerchio, K; Polvino, W; Gertz, B; Baylink, D; Mohan, S; Bengtsson, B A · RCT
MK-677 (25 mg/day for 8 weeks) increased 24-hour GH secretion rate by 1.8-fold, normalized pulsatile GH profiles, increased fat-free mass by ~3 kg, and raised basal metabolic rate in obese males.
Svensson, J; Lönn, L; Jansson, J O; Murphy, G; Wyss, D; Krupa, D; Cerchio, K; Polvino, W; Gertz, B; Boseaus, I; Sjöström, L; Bengtsson, B A · RCT
MK-677 increased bone formation markers at 2 and 12 months in healthy elderly and in hip fracture patients, with sustained IGF-1 elevation, demonstrating prolonged bone-building potential in age-related bone loss.
Murphy, M G; Bach, M A; Plotkin, D; Bolognese, J; Ng, J; Krupa, D; Cerchio, K; Gertz, B J · RCT
MK-677 increased IGF-1 through both GH-dependent and GH-independent mechanisms, and elevated cortisol through direct adrenal stimulation rather than ACTH, revealing multi-target pharmacology beyond simple GH secretagogue activity.
Schleim, K D; Jacks, T; Cunningham, P; Feeney, W; Frazier, E G; Niebauer, G W; Zhang, D; Chen, H; Smith, R G; Hickey, G · Animal Study
Structurally diverse GH secretagogues (peptides and non-peptides) all converge on the GHS receptor, whose cloning predicted the existence of a natural ligand — later identified as ghrelin — with widespread physiological roles beyond GH release.
Smith, R G; Palyha, O C; Feighner, S D; Tan, C P; McKee, K K; Hreniuk, D L; Yang, L; Morriello, G; Nargund, R; Patchett, A A; Howard, A D · Review
MK-677 increased serum leptin levels independent of body fat changes, increased testosterone, and had no effect on thyroid hormones in obese males, revealing metabolic effects dissociated from fat mass changes.
Svensson, J; Carlsson, B; Carlsson, L M; Jansson, J O; Bengtsson, B A · RCT
MK-677 produced mixed lipoprotein effects in obese males: beneficial increases in HDL and decreases in Lp(a), but also unfavorable increases in total cholesterol, LDL, and triglycerides over 8 weeks.
Svensson, J; Jansson, J O; Ottosson, M; Johannsson, G; Taskinen, M R; Wiklund, O; Bengtsson, B A · RCT
MK-677 at 10 and 25 mg/day increased GH and IGF-1 dose-dependently over 4 weeks in GH-deficient adults with acceptable safety, supporting its potential as oral GH replacement therapy.
Codner, E; Cassorla, F; Tiulpakov, A N; Mericq, M V; Avila, A; Pescovitz, O H; Svensson, J; Cerchio, K; Krupa, D; Gertz, B J; Murphy, G · Clinical Trial
MK-677 combined with alendronate maintained higher bone formation markers than alendronate alone over 12 months in postmenopausal women, demonstrating complementary mechanisms: IGF-1-stimulated bone building plus anti-resorptive bone protection.
Murphy, M G; Weiss, S; McClung, M; Schnitzer, T; Cerchio, K; Connor, J; Krupa, D; Gertz, B J · RCT
Ghrelin, hexarelin, and EP-80317 improved cardiac contractile recovery after ischemia in isolated rat hearts, with effects on coronary perfusion pressure, while MK-677 showed less cardioprotection — suggesting peptide GHS are preferred cardiac protectants.
Frascarelli, Sabina; Ghelardoni, Sandra; Ronca-Testoni, Simonetta; Zucchi, Riccardo · Animal Study
MK-677 treatment increased the proportion of non-22kDa and 20kDa GH isoforms relative to total GH in obese subjects, demonstrating that GH secretagogues alter the GH isoform profile differently from exogenous GH replacement.
Svensson, J; Boguszewski, C L; Shibata, F; Carlsson, B; Carlsson, L M S; Bengtsson, B-A · Clinical Trial
MK-677 increased GH and IGF-1 in elderly hip fracture patients with functional improvement trends, but the primary endpoint of functional independence was not statistically significant in this pilot RCT.
Bach, Mark A; Rockwood, Kenneth; Zetterberg, Carl; Thamsborg, Gorm; Hébert, Réjean; Devogelaer, Jean-Pierre; Christiansen, Jens Sandahl; Rizzoli, René; Ochsner, J Lockwood; Beisaw, Norman; Gluck, Oscar; Yu, Leisure; Schwab, Thomas; Farrington, Jeanne; Taylor, Alice M; Ng, Jennifer; Fuh, Vivian · RCT
MK-677, hexarelin, and other GH secretagogues demonstrated both direct GHS-R agonism and allosteric modulation of ghrelin binding — some enhancing (positive) and others reducing (negative) ghrelin's own receptor interaction, revealing complex biased pharmacology.
Holst, Birgitte; Brandt, Erik; Bach, Anders; Heding, Anders; Schwartz, Thue W · In Vitro
GH secretagogue development spans from GHRP-6 discovery through systematic optimization (hexarelin, GHRP-2, ipamorelin for selectivity; MK-677 for oral activity) to ghrelin identification as the natural ligand — two decades of reverse pharmacology driving clinical drug development.
Smith, Roy G · Review
Ghrelin receptor agonists demonstrate multi-system anti-aging potential: restoring GH/IGF-1 axis, improving body composition (lean mass/fat ratio), enhancing cardiac function, boosting immune competence, and supporting cognitive function in aging models — comprehensive geroscience intervention.
Smith, Roy G; Sun, Yuxiang; Jiang, Hong; Albarran-Zeckler, Rosie; Timchenko, Nikolai · Review
One year of oral MK-677 in healthy older adults (n=65) increased fat-free mass (+1.1 kg), GH, and IGF-1 but also increased fat mass, fasting glucose, and insulin resistance — the most comprehensive long-term RCT showing MK-677's mixed metabolic profile in aging.
Nass, Ralf; Pezzoli, Suzan S; Oliveri, Mary Clancy; Patrie, James T; Harrell, Frank E; Clasey, Jody L; Heymsfield, Steven B; Bach, Mark A; Vance, Mary Lee; Thorner, Michael O · RCT
MK-677 successfully increased GH/IGF-1 in AD patients but showed no clinical benefit on cognitive decline, ADAS-cog, or CDR-sb over the trial period — proving GH axis restoration alone is insufficient for treating established Alzheimer's disease.
Sevigny, J J; Ryan, J M; van Dyck, C H; Peng, Y; Lines, C R; Nessly, M L · RCT
GHS-R1a protein was decreased in brain areas and kidneys of hypertensive rats. Ghrelin reduced arterial pressure and increased renal artery conductance in SHR. GHS-R1a antagonism altered renal electrolyte handling in normal but not hypertensive rats, suggesting impaired receptor function in hypertension.
Sales da Silva, Elder; Ferreira, Patrícia Maria; Castro, Carlos Henrique; Pacheco, Lilian Fernanda; Graziani, Daniel; Pontes, Carolina Nobre Ribeiro; Bessa, Amanda de Sá Martins de; Fernandes, Erika; Naves, Lara Marques; Ribeiro, Larissa Cristina Dos Santos; Mendonça, Michelle Mendanha; Gomes, Rodrigo Mello; Pedrino, Gustavo Rodrigues; Ferreira, Reginaldo Nassar; Xavier, Carlos Henrique · Animal Study
Capromorelin activates the ghrelin receptor (GHSR), which is found on pancreatic delta cells that produce somatostatin. Activating delta cells was expected to suppress insulin secretion. On day 1: - Fasting blood glucose increased by 13 mg/dL (p < 0.0001) - Insulin decreased (p = 0.03) - Glucagon was unchanged - First-phase insulin response (FPIR) during glucose tolerance test dropped by 72% (from 17,437 to 4,931 ng/L/15min, p = 0.004) Days 2-4: - Mean interstitial glucose rose by 19 mg/dL (p = 0.03) - Glycemic variability increased (SD 9.7 vs 5.0, p = 0.02) By day 30: - Glucose tolerance returned to baseline - Glycemic variability normalized - But FPIR was still partially blunted (9,993 vs 17,437, p = 0.045) The body appeared to compensate for the initial insulin suppression over time.
Pires, J; Greathouse, R L; Quach, N; Huising, M O; Crakes, K R; Miller, M; Gilor, C · Animal Study