Muscle & Metabolism

AOD-9604 is a synthetic peptide fragment consisting of amino acids 176-191 from the C-terminus of human growth hormone (hGH) with a tyrosine residue added at the N-terminus. Developed by Metabolic Pharmaceuticals Limited, it was designed to mimic hGH's lipolytic (fat-burning) properties without stimulating IGF-1 production or causing insulin resistance. The peptide operates by activating beta-3 adrenergic receptors in adipose tissue, promoting lipolysis while inhibiting lipogenesis. Initial 12-week clinical trials showed modest weight loss (average 2.6 kg vs 0.8 kg placebo), but a larger 24-week trial of 536 subjects failed to demonstrate significant efficacy, leading to termination of development in 2007. Despite lack of FDA approval, AOD-9604 remains available through compounding pharmacies and gray market sources. It is prohibited by WADA as a non-approved substance under category S.0. The peptide has shown potential applications beyond obesity, including cartilage repair in osteoarthritis models.

GHRP-6 (Growth Hormone-Releasing Peptide-6) is a synthetic hexapeptide that functions as a potent growth hormone secretagogue, stimulating GH release from the pituitary gland primarily through hypothalamic mechanisms. It binds to two receptors (GHS-R1a and CD36), activating phosphatidylinositol second messenger systems and prosurvival pathways including PI-3K/AKT1. Beyond its GH-releasing properties, extensive preclinical research has demonstrated unexpected cytoprotective effects across multiple organ systems, including cardioprotective, neuroprotective, anti-fibrotic, and wound healing properties. Clinical studies have evaluated GHRP-6's safety and efficacy in various contexts, from growth stimulation in children to neuroprotection in stroke patients. Currently, GHRP-6 is not FDA-approved for therapeutic use and remains classified as a research peptide. It is banned by WADA for athletic competition. The compound is available through research chemical suppliers and compounding pharmacies, though its legal status varies by jurisdiction. The peptide has demonstrated a favorable safety profile in Phase I clinical trials with primarily mild adverse events.

CJC-1295 with DAC is a synthetic analog of growth hormone-releasing hormone (GHRH) developed by ConjuChem Biotechnologies, featuring a Drug Affinity Complex that binds to serum albumin for extended half-life of 6-8 days. Clinical trials demonstrated sustained increases in growth hormone (2-10 fold) for 6+ days and IGF-1 (1.5-3 fold) for 9-11 days after a single injection. The peptide was investigated in Phase 2 trials for HIV-associated lipodystrophy but was discontinued following a participant death, though it showed safety and tolerability in healthy adults at doses of 30-60 μg/kg.

Ipamorelin is a synthetic pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH₂) functioning as a selective growth hormone secretagogue that binds to ghrelin receptors (GHS-R1a) in the anterior pituitary to stimulate growth hormone release. Originally developed by Novo Nordisk, it represents the first GHRP-receptor agonist with selectivity for GH release comparable to GHRH, notably without stimulating cortisol or ACTH secretion even at doses 200-fold above therapeutic levels. While investigated in Phase II clinical trials for postoperative ileus (discontinued due to lack of efficacy), ipamorelin demonstrates promising preclinical effects on bone growth, muscle preservation, and metabolic function. Currently, it lacks FDA approval for any indication and exists in a regulatory gray area where it's marketed as a research chemical but widely used off-label in peptide therapy clinics for anti-aging, body composition optimization, and recovery enhancement, while simultaneously being prohibited by WADA as a performance-enhancing substance in competitive sports.

Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone (GHRH) that stimulates the production and secretion of endogenous growth hormone from the pituitary gland. The peptide consists of all 44 amino acids of human GHRH with the addition of a trans-3-hexenoic acid group at the N-terminus, which enhances its stability in serum. It was approved by the FDA in November 2010 under the brand name Egrifta as the first and only treatment specifically indicated for reducing excess visceral abdominal fat in HIV-infected patients with lipodystrophy. Clinical trials have demonstrated significant reductions in visceral adipose tissue (15-37% relative reduction), along with improvements in triglycerides, liver fat, and metabolic markers. The peptide has also shown promising effects on cognitive function in older adults and individuals with mild cognitive impairment. Tesamorelin is administered as a once-daily subcutaneous injection and is commercially available by prescription for its FDA-approved indication, though it remains under investigation for additional therapeutic applications including non-alcoholic fatty liver disease and age-related cognitive decline.

IGF-1 LR3 (Long R3 IGF-1) is a synthetic analog of human insulin-like growth factor-1 (IGF-1), featuring 83 amino acids with an arginine substitution at position 3 and an additional 13 amino acids at its N-terminus. These modifications reduce binding affinity to IGF-binding proteins by approximately 1000-fold, resulting in enhanced metabolic stability and a significantly longer half-life of 20-30 hours compared to native IGF-1. Research demonstrates that IGF-1 LR3 is 3-6 times more potent than natural IGF-1 in promoting cellular growth and protein synthesis through PI3K/Akt/mTOR signaling pathways. Primary research applications include studies on muscle hypertrophy, satellite cell activation, neurodegenerative diseases, and metabolic regulation. However, IGF-1 LR3 is not FDA-approved for any human therapeutic use and remains classified as a research chemical. It is prohibited by the World Anti-Doping Agency and most professional sports organizations. The compound is available only for laboratory research purposes, with CAS number 946870-92-4.

GHRP-2 (Pralmorelin) is a synthetic hexapeptide growth hormone secretagogue that acts as a ghrelin receptor (GHS-R) agonist to stimulate growth hormone release from the pituitary gland. It was the first peptide of this class introduced clinically and operates through a receptor pathway distinct from growth hormone-releasing hormone (GHRH). GHRP-2 has demonstrated potent GH-stimulating effects in both animal and human studies, with additional influences on appetite regulation and ACTH/cortisol secretion. The peptide is currently marketed by Kaken Pharmaceutical in Japan as a diagnostic agent for assessing growth hormone deficiency. Clinical trials have explored its therapeutic potential for treating GH deficiency, short stature, and critical illness, though development for therapeutic applications in the United States was discontinued. Beyond GH stimulation, research has identified cytoprotective properties including cardioprotective, antioxidant, and anti-inflammatory effects. GHRP-2 is well-tolerated in clinical studies with minimal side effects, though it remains primarily approved for diagnostic rather than therapeutic use outside of Japan.

CJC-1295 no DAC, also known as Modified GRF 1-29, is a synthetic analog of growth hormone-releasing hormone (GHRH) consisting of 29 amino acids with four strategic amino acid substitutions designed to enhance stability and bioactivity. Unlike CJC-1295 with DAC, this variant lacks the drug affinity complex, resulting in a shorter half-life of 30 minutes to 2 hours that promotes pulsatile growth hormone secretion mimicking natural physiological patterns. Research demonstrates it can increase growth hormone levels by 2- to 10-fold and IGF-1 concentrations by 1.5- to 3-fold in clinical trials. The peptide has been studied for potential applications in age-related GH decline, body composition optimization, and metabolic health. CJC-1295 no DAC is not FDA-approved for human use and is classified as a prohibited substance by WADA for athletic competition. It is available through compounding pharmacies for research purposes, though regulatory status remains uncertain following recent FDA actions on peptide compounding.

Sermorelin is a synthetic 29-amino acid peptide analogue of growth hormone-releasing hormone (GHRH), representing the shortest fully functional fragment of endogenous human GHRH. It stimulates the pituitary gland to produce and secrete natural growth hormone by binding to growth hormone-releasing hormone receptors (GHRHR). Unlike direct growth hormone replacement, sermorelin maintains physiological feedback regulation through somatostatin, promoting pulsatile hormone release that mirrors natural rhythms. Originally FDA-approved in 1997 as Geref for diagnosing and treating pediatric growth hormone deficiency, sermorelin demonstrated effectiveness in increasing height velocity in prepubertal children and served as a rapid diagnostic test for growth hormone insufficiency. Clinical research in adults has shown modest improvements in body composition, particularly increased lean mass in men, elevated IGF-1 levels, and potential benefits for sleep quality and cognitive function. The manufacturer discontinued production in 2008 for commercial reasons, though it remains available through compounding pharmacies for off-label use. While generally well-tolerated with minimal adverse effects, long-term safety data remains limited.