CJC-1295 With DAC Peptide

CJC-1295 DAC is a synthetic peptide that has been proposed to function in a manner similar to growth hormone-releasing hormone (GHRH), potentially stimulating the body’s endogenous production of growth hormone (GH). It is a 29-amino-acid analogue of GHRH and represents one of the shortest functional sequences capable of activating GH release from somatotroph cells in the pituitary gland.(1) Within this structure, four of the original amino acids have been substituted in CJC-1295 DAC, a modification intended to enhance its pharmacokinetic properties and extend its duration of action.

The DAC (Drug Affinity Complex) component is a biochemical modification designed to further prolong the peptide’s half-life. This effect is thought to result from the peptide’s ability to bind to plasma proteins. Specifically, the DAC involves the attachment of a lysine derivative—N-epsilon-3-maleimidopropionamide—to the C-terminus of the peptide. This structural modification may significantly extend the half-life of CJC-1295 DAC, with estimates suggesting a duration of up to approximately 8 days, while maintaining strong affinity for GHRH receptors comparable to that of CJC-1295 without DAC.(2)

This does not suggest that CJC-1295 without DAC lacks relevance in research contexts. For instance, combinations such as CJC-1295 without DAC paired with Ipamorelin have been explored for their potential synergistic effects. This approach combines a GHRH analogue with a peptide that may activate ghrelin receptors in the pituitary gland, which has been proposed to result in an enhanced growth hormone secretion response from somatotroph cells.(3)

Overview

CJC-1295 DAC is known by several interchangeable names, including CJC-1295, CJC-1295 with DAC, DAC:GRF, long-acting GHRH analogue, and synthetic GHRH analogue. As the peptide is considered a growth hormone-releasing factor, it has been studied for a range of potential effects associated with elevated endogenous growth hormone activity.

From a theoretical perspective, CJC-1295 DAC has been investigated for its potential role in reducing fat mass by promoting the use of stored fat as an energy source, while also supporting increases in muscle mass through enhanced protein synthesis. Additionally, given the role of growth hormone in bone development and connective tissue integrity, the peptide may contribute to improved bone density and a reduced risk of structural damage.

Research has also suggested that GHRH may influence neural centres associated with sleep regulation, and it has been proposed that this effect could be reflected in analogues such as CJC-1295 DAC, potentially supporting sleep-related processes.(4)

Chemical Makeup
  • Molecular Formula: C152H252N44O42
  • Molecular Weight: 3367.95 g/mol
  • Other Known Titles: Tetra substituted GRF 1-29 with DAC
Research and Clinical Studies
CJC-1295 DAC Peptide Mechanism of Action

Researchers conducted two clinical studies in 2006 to evaluate the activity of CJC-1295 DAC. In the first study, the peptide or a placebo was administered in four ascending concentrations, while in the second study, it was administered repeatedly at a single concentration. The findings indicated that exposure to CJC-1295 DAC appeared to result in increased levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) within the research models.(5) 

CJC-1295 DAC is proposed to elevate IGF-1 levels through stimulation of growth hormone production, which may subsequently bind to receptors on liver cells and initiate intracellular signalling cascades. This interaction is thought to activate the Janus kinase–signal transducer and activator of transcription (JAK-STAT) pathway, potentially leading to transcription of the IGF-1 gene. The IGF-1 produced in the liver may then be distributed to various tissues, while local IGF-1 production may also occur in tissues containing GH receptors. IGF-1 is considered a key mediator of growth-related processes, potentially supporting cellular proliferation, tissue enlargement, and protein synthesis. Experimental observations suggest that CJC-1295 DAC exposure may increase average GH levels by approximately 2- to 10-fold for several days, while IGF-1 levels may rise by 1.5- to 3-fold and remain elevated for extended periods, particularly with repeated exposure.(5) 

Further investigation into GH pulsatility following a single administration of CJC-1295 DAC indicated an approximate 50% increase in mean GH secretion and IGF-1 levels. Researchers also suggested that peak GH levels may increase by up to 7.5 times under certain conditions.(6) It is believed that CJC-1295 DAC interacts with binding sites on the GHRH receptor, potentially altering its structure and activating intracellular G-proteins. This activation may lead to the production of secondary messengers such as cyclic adenosine monophosphate (cAMP) and inositol trisphosphate (IP3), which play important roles in cellular signalling. These messengers may subsequently activate protein kinases that regulate gene expression by phosphorylating transcription factors, ultimately influencing growth hormone production within somatotroph cells.(7)(8) 

Additional animal studies have explored the broader physiological effects of CJC-1295 DAC. In murine models, daily administration of the peptide appeared to normalise growth patterns, while less frequent dosing produced intermediate effects, suggesting a potential interval-dependent response.(9) The findings also indicated possible improvements in body composition, including increased muscle hypertrophy and stable or reduced fat mass. In models lacking the GHRH gene, CJC-1295 DAC exposure appeared to preserve lean mass and prevent excess fat accumulation. Furthermore, increases in pituitary RNA and GH mRNA levels were observed, suggesting enhanced activity or proliferation of somatotroph cells. These findings support the hypothesis that CJC-1295 DAC may influence growth hormone regulation and downstream physiological processes through multiple interconnected mechanisms.(9)

CJC-1295 DAC Peptide Half-life

In its modified form, CJC-1295 DAC incorporates a technology known as Drug Affinity Complex (DAC).(1) In contrast to native growth hormone-releasing hormone (GHRH), which has a relatively short half-life of approximately 7 minutes, CJC-1295 without DAC has been reported to exhibit a longer half-life of around 30 minutes. This extension is attributed to its truncated 29-amino-acid structure, in which four of the original amino acids have been strategically substituted to improve stability.

These structural modifications occur at specific positions within the peptide sequence and are designed to enhance resistance to enzymatic degradation, particularly by dipeptidyl peptidase-4. At position 2, L-alanine is replaced with D-alanine, a change believed to increase resistance to enzymatic breakdown. At position 8, asparagine is substituted with glutamine, which may reduce the likelihood of molecular rearrangement and hydrolysis. At position 15, glycine is replaced with alanine, a modification thought to improve bioactivity. Finally, at position 27, methionine is substituted with leucine, which may help prevent oxidative degradation of the peptide.

Collectively, these alterations are intended to improve the peptide’s structural stability and functional performance under physiological conditions. In addition to these modifications, the inclusion of DAC technology further extends the peptide’s half-life, with estimates suggesting a duration of approximately 6 to 8 days.(10)

CJC-1295 DAC Peptide Ancillary Studies

In 2005, a clinical study was initiated to investigate the mechanism of action of CJC-1295 DAC in models of immunodeficiency virus (HIV) associated with visceral obesity. The study design involved administering the peptide over a three-month period, followed by a six-week follow-up phase. However, the trial was discontinued during the recruitment stage, and as a result, no findings or outcomes were reported.(11)

In a separate investigation conducted in 2009, researchers at the Norwegian Doping Control Laboratory and the School of Pharmacy analysed a submitted compound to determine whether it contained any prohibited substances. Their analysis identified the compound as CJC-1295 DAC. In their published findings, the researchers concluded that “CJC-1295 DAC is a releasing factor for growth hormone,” reinforcing its classification as a compound capable of influencing growth hormone activity.(1)

CJC-1295 DAC peptide is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. Henninge J, Pepaj M, Hullstein I, Hemmersbach P. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Testing and Analysis. 2010 Nov-Dec;2(11-12):647-650.  DOI: 10.1002/dta.233.

  2. Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. 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. 2005 Jul;146(7):3052-8. doi: 10.1210/en.2004-1286. Epub 2005 Apr 7. PMID: 15817669.

  3. Sinha DK, Balasubramanian A, Tatem AJ, Rivera-Mirabal J, Yu J, Kovac J, Pastuszak AW, Lipshultz LI. Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Transl Androl Urol. 2020 Mar;9(Suppl 2):S149-S159. doi: 10.21037/tau.2019.11.30. PMID: 32257855; PMCID: PMC7108996.

  4. Steiger A, Holsboer F. Neuropeptides and human sleep. Sleep. 1997 Nov;20(11):1038-52. PMID: 9456470.

  5. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. J Clin Endocrinol Metab. 2006 Mar;91(3):799-805.  doi: 10.1210/jc.2005-1536.  Epub 2005 Dec 13. PMID: 16352683. 

  6. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006 Dec;91(12):4792-7.  doi: 10.1210/jc.2006-1702.  Epub 2006 Oct 3. PMID: 17018654.

  7. Martin, B., Lopez de Maturana, R., Brenneman, R., Walent, T., Mattson, M. P., & Maudsley, S. (2005). Class II G protein-coupled receptors and their ligands in neuronal function and protection. Neuromolecular medicine, 7(1-2), 3–36.  https://doi.org/10.1385/nmm:7:1-2:003

  8. Newton, A. C., Bootman, M. D., & Scott, J. D. (2016). Second Messengers. Cold Spring Harbor perspectives in biology, 8(8), a005926.   https://doi.org/10.1101/cshperspect.a005926

  9. Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1290-4.  doi: 10.1152/ajpendo.00201.2006.  Epub 2006 Jul 5. PMID: 16822960.

  10. Van Hout MC, Hearne E. Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions. Subst Use Misuse. 2016 Jan 2;51(1):73-84.  doi: 10.3109/10826084.2015.1082595.  Epub 2016 Jan 15. PMID: 26771670.

  11. ClinicalTrials.gov, A service of the US National Institutes of Health. Available at:  http://clinicaltrials.gov/ct2/show/NCT00267527  (27 June 2010).

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

CJC-1295 With DAC Peptide