CJC-1295 Peptide (No DAC)

CJC-1295 is a synthetic peptide derived from the naturally occurring growth hormone-releasing hormone (GHRH) and consists of a 29-amino-acid sequence.(2) It is also commonly referred to as Modified GRF (1-29) or CJC-1295 without DAC. This version incorporates four amino acid substitutions that are intended to reduce susceptibility to enzymatic degradation, thereby improving peptide stability. Unlike its DAC-modified counterpart, CJC-1295 without DAC does not include a Drug Affinity Complex, which is otherwise used to further extend the peptide’s half-life.

Modified growth hormone fragments such as GRF (1-29) were first identified in the early 1980s, when it was proposed that the initial 29 amino acids of the native 44-amino-acid GHRH peptide retained its full biological activity.(3) A recognised limitation of early synthetic GHRH peptides was their short half-life. Subsequent research has focused on stabilising these fragments, leading to the development of longer-lasting variants such as CJC-1295 without DAC, which are designed to offer improved durability while maintaining functional activity.(1)

Overview

CJC-1295 without DAC, also referred to as tetra-substituted GRF (1-29), is a synthetic analogue of the naturally occurring growth hormone-releasing hormone (GHRH). It has been proposed to support the secretion of growth hormone (GH) by interacting with GHRH receptors. This peptide is constructed from the minimal amino acid sequence required for receptor binding, specifically the first 29 amino acids of the native GHRH structure.

Key structural differences distinguish CJC-1295 without DAC from the unmodified GHRH fragment, primarily due to substitutions at four positions within the 29-amino-acid chain. These modifications occur at the 2nd, 8th, 15th, and 27th amino acids, and are thought to enhance resistance to enzymatic degradation—particularly from enzymes such as dipeptidyl peptidase-4 (DPP-4).(4) As a result, these alterations may improve the peptide’s stability and extend its functional lifespan under physiological conditions.

More specifically, these alterations include:

  • The replacement of L-alanine with D-alanine at the 2nd position, which is thought to bolster resistance against molecular degradation.
  • The substitution of asparagine with glutamine at the 8th position, which could conceivably minimize asparagine reconfiguration and amide hydrolysis.
  • The exchange of glycine for alanine at the 15th position, which is speculated to enhance bioactivity.
  • The alteration from methionine to leucine at the 27th position, which is suggested to prevent methionine oxidation.
Chemical Makeup
  • Molecular Formula: C152H252N44O42
  • Molecular Weight: 3367.9 g/mol
  • Other Known Titles: CJC-1295 Without DAC 
Research and Clinical Studies
CJC-1295 (No DAC) Peptide and the Pituitary Gland

CJC-1295 without DAC is proposed to act on GHRH receptors located on pituitary cells, potentially interacting with specific binding sites on the receptor. This interaction may lead to conformational changes in the receptor structure, initiating a cascade of intracellular events that activate signalling pathways within the target cells. These structural alterations are thought to promote the activation of G-proteins, which are signalling molecules situated on the الداخلي side of the GHRH receptor.(5)

Once activated, these G-proteins may stimulate the production of secondary messengers such as cyclic adenosine monophosphate (cAMP) and inositol trisphosphate (IP3), which function as intracellular signalling intermediaries and may amplify the cellular response. In particular, cAMP is believed to activate protein kinases—enzymes that play a central role in phosphorylating specific target proteins.(6) These protein kinases are involved in regulating various cellular functions, including the activation of transcription factors that control gene expression.

Following phosphorylation, these transcription factors may translocate into the nucleus, where they could influence the expression of genes associated with the synthesis and release of growth hormone. As a result, the sequence of molecular events initiated by the binding of CJC-1295 without DAC may ultimately lead to the fusion of growth hormone-containing secretory vesicles with the cell membrane. This process facilitates the release of growth hormone from pituitary cells, allowing it to enter circulation and exert its physiological effects.

CJC-1295 (No DAC) Peptide and Growth Hormone Pulsatility

While there are no studies directly examining the specific effects of CJC-1295 without DAC (tetra-substituted GRF 1-29), researchers have conducted investigations using partially modified versions of GRF (1-29). One such example is the work by Khorram et al., which explored the peptide’s potential impact on growth hormone (GH) and insulin-like growth factor-1 (IGF-1), as well as outcomes related to skin cell proliferation, muscle hypertrophy, and related physiological effects.(7)

The findings suggested that CJC-1295 without DAC may influence the GH–IGF-1 axis. More specifically, the peptide appeared to increase the average 12-hour release of growth hormone from somatotroph cells in the anterior pituitary by approximately 70–107%. In parallel, IGF-1 levels were reported to increase by around 28%, indicating enhanced activity within this hormonal pathway. These changes were also associated with increased skin thickness, potentially reflecting the anabolic effects of GH and IGF-1 on collagen-producing cells such as fibroblasts. Additionally, a notable increase in muscle hypertrophy was observed, resulting in an approximate lean mass gain of 2.77 lbs.

These findings suggest that CJC-1295 without DAC may play a role in supporting skin cell proliferation and muscle tissue development. However, the precise mechanisms underlying these effects remain unclear and warrant further investigation in future studies.

CJC-1295 (No DAC) Peptide and Intestinal Studies

Studies conducted in experimental models have suggested a potential interaction between GHRH analogue peptides and VPAC(1)-R receptors located on the smooth muscle of the gastrointestinal system.(8) This interaction has been proposed to influence bowel motility, potentially promoting intestinal movement. However, the specific relationship between individual peptides and their effects on bowel function remains under investigation and has yet to be fully established.

CJC-1295 (No DAC) Peptide and Heart Rate

Preliminary research in murine models has suggested that Modified GRF (1-29) peptides, along with other GHRH analogue compounds, may have the potential to influence cardiac function following injury.(9) Observations from the study indicated that these peptides may contribute to improvements in heart rate and support the heart’s ability to pump blood, particularly in the context of post–heart attack recovery.

The researchers further noted that GHRH agonist peptides appeared to promote cardiac tissue repair and may also enhance ejection fraction, suggesting a possible role in improving overall cardiac performance. However, these findings remain preliminary and require further investigation.

CJC-1295 (No DAC) Peptide and Combination

CJC-1295 without DAC is considered a relatively short-acting GHRH analogue when compared to longer-lasting modified variants that include DAC. As a result, when used alongside other short-acting peptides, it may contribute to extended or more sustained functional effects. Additionally, the peptide has been suggested to exhibit synergistic potential when combined with growth hormone secretagogues (GHSs). These compounds are regarded as ghrelin mimetics, interacting with ghrelin receptors located across various tissues, including somatotroph cells in the anterior pituitary gland—the same cells that express GHRH receptors and are responsible for growth hormone synthesis.

Activation of these ghrelin receptors may lead to increased growth hormone production, and some researchers propose that simultaneous stimulation of both GHRH and ghrelin receptors on somatotroph cells may result in a synergistic enhancement of growth hormone release.(11) One commonly referenced combination is CJC-1295 with Ipamorelin, a synthetic peptide that acts via the ghrelin receptor pathway. While both peptides are suggested to promote growth hormone secretion, they do so through different mechanisms, which may contribute to a more pronounced overall effect when used together.

CJC-1295 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. National Center for Biotechnology Information. "PubChem Compound Summary for CID 91976842, CJC1295 Without DAC" PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/CJC1295-Without-DAC

  2. Clark, R G, and I C Robinson. “Growth induced by pulsatile infusion of an amidated fragment of human growth hormone releasing factor in normal and GHRF-deficient rats.” Nature vol. 314,6008 (1985): 281-3. https://pubmed.ncbi.nlm.nih.gov/2858818/

  3. The Discovery of Growth Hormone-Releasing Hormone: An Update  https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2826.2008.01740.x

  4. 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

  5. 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

  6. Khorram, O., Laughlin, G. A., & Yen, S. S. (1997). Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. The Journal of clinical endocrinology and metabolism, 82(5), 1472–1479.  https://doi.org/10.1210/jcem.82.5.3943

  7. Ito T, Igarashi H, Pradhan TK, Hou W, Mantey SA, Taylor JE, Murphy WA, Coy DH, Jensen RT. GI side-effects of a possible therapeutic GRF analogue in monkeys are likely due to VIP receptor agonist activity. Peptides. 2001 Jul, 22(7):1139-51.   https://pubmed.ncbi.nlm.nih.gov/11445245/

  8. Schally AV, Zhang X, Cai R, Hare JM, Granata R, Bartoli M. Actions and Potential Therapeutic Applications of Growth Hormone-Releasing Hormone Agonists. Endocrinology. 2019 Jul 1;160(7):1600-1612.  https://pubmed.ncbi.nlm.nih.gov/31070727/

  9. Sinha, D. K., Balasubramanian, A., Tatem, A. J., Rivera-Mirabal, J., Yu, J., Kovac, J., Pastuszak, A. W., & Lipshultz, L. I. (2020). Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males. Translational andrology and urology, 9(Suppl 2), S149–S159.   https://doi.org/10.21037/tau.2019.11.30

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 Peptide (No DAC)