Research Use Only: This product is supplied for laboratory research and in-vitro studies. Not for human or veterinary administration.
CJC-1295 With DAC (5mg)
- GHRH Analog with DAC: 30-amino acid peptide with albumin-binding technology, ≥98% purity
- Extended Half-Life: 5.8-8.1 day biological half-life via maleimide-albumin conjugation
- GH/IGF-1 Axis Research: Sustained 2-10 fold GH and 1.5-3 fold IGF-1 elevation studies
- Mechanistic pathway studies
- In vitro receptor profiling
- HPLC verified identity and purity
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Research Overview
CJC-1295 with Drug Affinity Complex (DAC), also designated DAC:GRF, is a 30-amino acid synthetic analog of human growth hormone-releasing hormone (GHRH) engineered for markedly extended plasma persistence. Developed by ConjuChem Biotechnologies (Montreal, Canada) and first characterized in 2005, CJC-1295 DAC incorporates four strategic amino acid substitutions to resist enzymatic degradation and a C-terminal maleimidopropionyl-lysine moiety (the Drug Affinity Complex) that forms a covalent thioether bond with serum albumin Cys-34 upon subcutaneous injection. This albumin conjugation extends the compound's biological half-life from approximately 30 minutes (for the non-DAC analog) to 5.8-8.1 days, representing a greater than 10,000-fold increase in plasma persistence relative to native GHRH.
Clinical investigation of CJC-1295 DAC has generated a focused but significant body of peer-reviewed literature. Pivotal human trials published in the Journal of Clinical Endocrinology & Metabolism demonstrated sustained, dose-dependent increases in growth hormone (GH) concentrations of 2- to 10-fold for six or more days, and insulin-like growth factor-1 (IGF-1) elevations of 1.5- to 3-fold persisting 9-11 days after a single injection. The estimated biological half-life was 5.8-8.1 days. Importantly, Ionescu and Frohman (2006) demonstrated that despite continuous GHRH receptor stimulation by CJC-1295, pulsatile GH secretion was preserved: basal (trough) GH levels increased 7.5-fold (P < 0.0001), overall mean GH levels increased by 46% (P < 0.01), and GH pulse frequency and amplitude remained unaltered.
CJC-1295 DAC advanced to Phase II clinical trials for HIV-associated lipodystrophy (ClinicalTrials.gov NCT00267527) before the program was terminated in 2006. Today, the compound remains a valuable research tool for investigating GHRH receptor signaling, somatotroph biology, long-acting peptide drug design, and GH/IGF-1 axis pharmacology. It is classified under Section S2 of the World Anti-Doping Agency (WADA) Prohibited List as a growth hormone-releasing hormone analog.
Primary Research Applications
Mechanism of Action
GHRH Receptor Activation and cAMP/PKA Signaling
GHRH-R Activation — CJC-1295 DAC exerts its primary biological effects through high-affinity binding to the growth hormone-releasing hormone receptor (GHRH-R), a class B1 G-protein coupled receptor (GPCR) expressed predominantly on somatotroph cells of the anterior pituitary gland. Upon ligand binding, GHRH-R couples to the stimulatory G-protein alpha subunit (Gαs), activating adenylyl cyclase and increasing intracellular cyclic adenosine monophosphate (cAMP). Elevated cAMP activates protein kinase A (PKA), which phosphorylates the transcription factor CREB (cAMP response element-binding protein). Phosphorylated CREB induces expression of the pituitary-specific transcription factor Pit-1, which in turn drives transcription of the growth hormone gene (GH1), leading to both synthesis and secretion of GH from somatotroph cells.
Sustained GH/IGF-1 Axis Stimulation via Albumin Conjugation
DAC-Albumin Reservoir — The DAC modification fundamentally alters the pharmacokinetic and pharmacodynamic profile of CJC-1295 compared to both native GHRH and the non-DAC analog. Upon subcutaneous injection, the maleimide group on Lys³⁰ rapidly conjugates to albumin Cys-34, creating a circulating peptide-albumin reservoir that slowly dissociates and activates pituitary GHRH-R over days rather than minutes. Single subcutaneous injections produced dose-dependent GH elevations of 2- to 10-fold persisting for six or more days, and IGF-1 increases of 1.5- to 3-fold lasting 9-11 days. This pharmacokinetic profile produces a shift from the pulsatile GH release pattern characteristic of native GHRH to a more sustained, tonic GH elevation while maintaining the physiological pulsatile pattern and intact somatostatin-mediated negative feedback mechanisms.
Somatotroph Trophic Effects and Proliferation
Pituitary Cell Growth — Beyond acute GH secretagogue activity, CJC-1295 demonstrates trophic effects on pituitary somatotroph cells. In GHRH knockout (GHRHKO) mice lacking endogenous GHRH signaling, daily administration of CJC-1295 for five weeks produced significant somatotroph cell proliferation confirmed by immunohistochemistry. Treatment increased total pituitary RNA content and GH mRNA expression, indicating both cellular proliferation and enhanced biosynthetic capacity. Daily dosing normalized body weight, body length, and femur/tibia dimensions in these growth-deficient animals. However, research by Ben-Shlomo et al. (2020) demonstrated that chronic cAMP elevation from sustained GHRH-R stimulation can induce DNA damage markers (phosphorylated gamma-H2AX) in somatotroph cells in a dose-dependent manner, suggesting that prolonged overstimulation may carry proliferative risks.
“Mechanistic summaries on this page are provided for laboratory reference and should be interpreted within controlled experimental settings only.”
Preclinical Research Summary
In the pivotal human clinical trial by Teichman et al. (2006), two randomized, placebo-controlled, double-blind, ascending dose studies in healthy adults aged 21-61 demonstrated that single subcutaneous injections of CJC-1295 DAC produced dose-dependent GH increases of 2- to 10-fold persisting for six or more days, and IGF-1 increases of 1.5- to 3-fold lasting 9-11 days. The estimated biological half-life was 5.8-8.1 days. No serious adverse reactions were reported, with the most frequently reported adverse events being transient injection site reactions consisting of pain, swelling, induration, and occasionally localized urticaria. Mild and transitory systemic effects including flushing, water retention, and changes in sleep patterns were also reported.
Ionescu and Frohman (2006) conducted overnight 12-hour blood sampling (20-minute intervals) in healthy men aged 20-40 before and 1 week after CJC-1295 injection (60 or 90 µg/kg). Results demonstrated that basal GH increased 7.5-fold (P < 0.0001), mean GH increased 46% (P < 0.01), and IGF-1 increased 45% (P < 0.001). Crucially, GH pulse frequency and amplitude remained unaltered, indicating that CJC-1295 enhances the baseline GH secretory tone while maintaining the physiological pulsatile pattern. In preclinical studies, Alba et al. (2006) showed that daily CJC-1295 administration in GHRH knockout mice normalized body weight, body length, and bone dimensions over five weeks, with confirmed somatotroph cell proliferation by immunohistochemistry.
Research by Ben-Shlomo et al. (2020) identified a potential concern: chronic CJC-1295 treatment in mouse models induced dose-dependent DNA damage markers in somatotroph cells and produced a 47% increase in pituitary weight over eight weeks, raising theoretical concerns about prolonged supraphysiologic GHRH-R stimulation. While these results are promising in demonstrating the compound's biological activity and mechanism of action, it is important to note that the Phase II trial was terminated in 2006 before completion, and comprehensive long-term safety data from controlled studies remain limited.
Academic References
- Jette L, Leger R, Thibaudeau K, et al. (2005). Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology.
- Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA (2006). Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. Journal of Clinical Endocrinology & Metabolism.
- Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R (2006). Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American Journal of Physiology - Endocrinology and Metabolism.
- Ionescu M, Frohman LA (2006). Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology & Metabolism.
- Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ (2009). Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth Hormone & IGF Research.
- Ben-Shlomo A, Deng N, Ding E, Yamamoto M, Mamelak A, Chesnokova V, Labadzhyan A, Melmed S (2020). DNA damage and growth hormone hypersecretion in pituitary somatotroph adenomas. Journal of Clinical Investigation.
- Memdouh S, Gavrilovic I, Ng K, Cowan D, Abbate V (2021). Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug Testing and Analysis.
- Knoop A, Thomas A, Fichant E, et al. (2016). Qualitative identification of growth hormone-releasing hormones in human plasma by means of immunoaffinity purification and LC-HRMS/MS. Analytical and Bioanalytical Chemistry.
- Timms M, Ganio K, Steel R (2019). A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS. Drug Testing and Analysis.
- ClinicalTrials.gov (2006). A Study to Evaluate CJC 1295 in HIV Patients With Visceral Obesity. NCT00267527.
This product is intended exclusively for in vitro laboratory research by qualified professionals. Not for human consumption. Not approved by the FDA.
Published Research Briefs
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