GH Secretagogues

CJC-1295 is a synthetic peptide analogue of growth hormone-releasing hormone (GHRH), specifically a modified version of the first 29 amino acids of endogenous GHRH (GRF 1-29). The peptide incorporates four amino acid substitutions that confer resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV), which normally cleaves and inactivates native GHRH within minutes. CJC-1295 exists in two forms: with a Drug Affinity Complex (DAC) that binds serum albumin to extend half-life to approximately 6-8 days, and without DAC (commonly called Mod GRF 1-29) which retains a shorter half-life of roughly 30 minutes. The peptide was developed by ConjuChem Biotechnologies and reached Phase II clinical trials for growth hormone deficiency and lipodystrophy before development was discontinued. It remains one of the most studied GHRH analogues and is frequently used in research settings, often in combination with GH-releasing peptides (GHRPs) to produce synergistic GH release through dual receptor activation.

GHRP-2 (growth hormone releasing peptide-2), marketed in Japan as pralmorelin (Grelin), is a synthetic hexapeptide GH secretagogue that stimulates pulsatile GH release by activating the ghrelin receptor (GHS-R1a). It is approved in Japan for the diagnosis of GH deficiency and was in Phase 2 development in the United States before Wyeth discontinued the program. GHRP-2 is widely used in research and compounding contexts as a GH secretagogue. Unlike ipamorelin — which selectively stimulates GH with minimal cortisol/ACTH co-activation — GHRP-2 activates both the GH axis and the HPA axis (ACTH/cortisol) via dual PKA and PKC signaling pathways in pituitary cells. This dual activation makes GHRP-2 useful as a two-in-one diagnostic tool (simultaneous GH + secondary adrenal insufficiency testing) but reduces its selectivity as a GH secretagogue relative to ipamorelin.

GHRP-6 (growth hormone releasing peptide-6) is the prototype synthetic GH secretagogue hexapeptide, discovered by Bowers et al. in the 1980s through systematic structure-activity optimization of enkephalin analogs. It was the founding member of a class of compounds that ultimately led to the discovery of the endogenous ghrelin system (ghrelin is the natural ligand for the GHS-R1a receptor that GHRP-6 activates). GHRP-6 is a research compound with no approved therapeutic indication. Its primary research interest is in GH stimulation for growth hormone deficiency investigation and, separately, in GH-independent cytoprotective and anti-fibrotic effects via CD36 receptor activation. It is less selective than newer GHRPs (ipamorelin, GHRP-2) and produces more pronounced appetite stimulation and cortisol co-activation.

Hexarelin (examorelin) is a synthetic hexapeptide GH secretagogue and the most potent GHS-R1a agonist in its structural class. It was developed by Europeptides in the 1990s as an optimized analog of GHRP-6, incorporating a 2-methyl-tryptophan (D-2-MeTrp) at position 2 to enhance receptor binding affinity and metabolic stability. Despite its potency, hexarelin has no regulatory approval and is classified as a research compound. Hexarelin occupies a unique position among GHRPs: it has the highest absolute GH release potency in humans, verified in dose-response trials, while simultaneously demonstrating GH-independent cardioprotective effects via CD36 receptor activation on cardiomyocytes. This dual mechanism — GHS-R1a stimulation for GH release and CD36 for cardiac protection — makes hexarelin a pharmacologically distinctive research tool.

IGF-1 LR3 (Long R3 Insulin-like Growth Factor-1) is a synthetic analog of human insulin-like growth factor 1 (IGF-1) designed for extended bioavailability. It consists of the full 70-amino acid IGF-1 sequence plus a 13-amino acid N-terminal extension, with a single amino acid substitution (Glu³ → Arg) that reduces binding affinity for IGF-binding proteins (IGFBPs) by approximately 500-fold. IGF-1 LR3 is a research compound with no approved indication for human therapeutic use. It is used extensively in cell culture research (as a superior alternative to native IGF-1 for in vitro growth factor supplementation) and in preclinical animal studies. Despite widespread use in performance enhancement communities, no human clinical trials of IGF-1 LR3 have been published. Note: IGF-1 LR3 is a large recombinant protein (83 amino acids, ~9.1 kDa) — technically at the upper boundary of the "peptide" classification. It is categorized with GH axis peptides by research vendors due to its role in GH/IGF-1 axis signaling.

Ipamorelin is a synthetic pentapeptide growth hormone secretagogue (GHS) that stimulates pituitary growth hormone (GH) release through agonism of the ghrelin/GHS-R1a receptor. Developed by Novo Nordisk in the late 1990s, it was the first GHS demonstrated to selectively release GH without concomitant stimulation of ACTH, cortisol, or prolactin at physiological doses. This selectivity profile distinguishes it from earlier GHS peptides such as GHRP-6 and hexarelin. Ipamorelin has been investigated in human clinical trials, most notably a Phase II study for postoperative ileus following abdominal surgery. While it demonstrated a favorable safety profile in that context, it did not meet its primary efficacy endpoint and development for that indication was not advanced. It remains of significant research interest as a tool compound for studying GH axis physiology and as a potential therapeutic in age-related GH decline.

MGF (Mechano Growth Factor) is a splice variant of insulin-like growth factor 1 (IGF-1) generated in mechanically stressed muscle tissue (exercise, loading, injury). The full-length MGF transcript (IGF-1Ec) is produced by alternative splicing of the IGF-1 gene; its C-terminal E-domain encodes a unique 24-amino acid peptide that is proteolytically cleaved to act independently of the IGF-1 receptor. The sequence listed above is the MGF E-domain C-terminal peptide — the form sold by research peptide vendors. MGF differs from mature IGF-1 in two key respects: it is locally produced in mechanically stressed tissue (not systemically circulated like liver-derived IGF-1), and the E-domain peptide activates satellite cells (muscle stem cells) through a receptor distinct from IGF-1R. This local, mechanosensitive satellite cell activation mechanism is proposed as a critical step in muscle repair and hypertrophy that declines with aging. MGF is WADA-monitored (detected in anti-doping testing) and has no approved therapeutic indication.

PEG-MGF (pegylated mechano growth factor) is the PEGylated form of the MGF E-domain peptide (see MGF entry). PEGylation — attachment of polyethylene glycol chains to the peptide — is a pharmaceutical strategy to reduce renal clearance and proteolytic degradation, extending the plasma half-life of short peptides from minutes to hours or days. **Evidence status:** No peer-reviewed PubMed-indexed studies for "PEG-MGF" as a named compound have been published. All evidence for PEG-MGF must be extrapolated from: 1. The parent MGF E-domain peptide pharmacology (see MGF entry) 2. General PEGylated peptide pharmacokinetic principles The molecular weight varies with PEG chain length; commercially sold PEG-MGF typically adds 1–5 kDa PEG to the ~2.87 kDa MGF E-domain, resulting in a compound of approximately 4–8 kDa. Molecular weight and formula fields cannot be precisely specified and are listed as not applicable.

Sermorelin is a synthetic peptide comprising the first 29 amino acids of endogenous growth hormone-releasing hormone (GHRH). It was FDA-approved in 1997 under the brand name Geref (Serono) for the diagnosis of growth hormone deficiency in children and for GH secretion stimulation tests. The branded product was withdrawn from the US market in 2002 for commercial reasons unrelated to safety or efficacy. It is currently available through licensed compounding pharmacies and is widely used off-label for adult growth hormone insufficiency. Sermorelin differs from exogenous recombinant human GH (rhGH) in a key way: it stimulates endogenous GH production from the pituitary rather than replacing it. This preserves the hypothalamic-pituitary feedback loop, prevents receptor desensitization, and maintains pulsatile GH secretion — the natural pattern associated with anabolic effects. Sermorelin is WADA-prohibited in competitive sports.

Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone (GHRH) consisting of the full 44-amino acid hGRF(1-44) sequence modified with a trans-3-hexenoic acid group at the N-terminus. This modification confers resistance to enzymatic degradation while preserving full GHRH receptor agonist activity. Developed by Theratechnologies, tesamorelin is the only GHRH analogue approved by the FDA (as Egrifta) for the treatment of excess abdominal fat in HIV-infected patients with lipodystrophy. Tesamorelin occupies a unique position among GH secretagogues as the only one with an FDA-approved indication. Its mechanism preserves the physiological pulsatile pattern of GH secretion, unlike exogenous GH administration which produces supraphysiological, non-pulsatile levels. Recent research has expanded interest beyond HIV lipodystrophy to include non-alcoholic fatty liver disease (NAFLD), where tesamorelin has demonstrated hepatoprotective effects potentially independent of its visceral fat-reducing properties.