CJC-1295 DAC Peptide (5mg)

General Description

CJC-1295 DAC is recognized by many names: CJC-1295, CJC-1295 with DAC, DAC:GRF, long-acting GHRH analog, and synthetic GHRH analog. Theoretically, since the peptide is considered a growth hormone-releasing factor, CJC-1295 DAC has been studied for its potential role in:

• The reduction of fat mass through the use of fat cells as an energy source. It may lead to an increase in muscle mass through the promotion of protein synthesis.
• Since growth hormone is considered to promote bone growth and the improvement of joint and connective tissue, the CJC-1295 DAC peptide may potentially improve bone mass and therefore reduce the risk of damage.
• Studies have suggested that GHRH may support centers in the nervous system for sleep, and potentially this action may be mirrored by analogs like CJC-1295 DAC.(4)

Chemical Composition

• Molecular Formula: C152H252N44O42
• Molecular Weight: 3367.95 g/mol
• Other Known Titles: Tetrasubstituted GRF 1-29 with DAC

Mechanism of Action of CJC-1295 DAC Peptide

Researchers conducted two clinical studies in 2006 to examine the action of CJC-1295 DAC. In the first study, CJC-1295 DAC or a placebo was presented in one of four ascending concentrations. In the second study, CJC-1295 DAC was presented repeatedly at a single concentration. According to the results, after the introduction of CJC-1295 DAC, there appeared to be an increase in GH and insulin-like growth factor-1 (IGF-I) levels among the research models.(5) It is believed that CJC-1295 DAC elevates IGF-1 levels by increasing growth hormone production, which in turn can bind to receptors in liver cells, potentially triggering a cascade of intracellular signaling processes. This binding could activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway. Subsequently, activated STAT proteins could migrate to the nucleus, where they may bind to specific DNA sequences considered response elements, possibly resulting in the transcription of the IGF-I gene. It is theorized that IGF-I produced in liver cells can be transported to various target tissues. Furthermore, it is believed that many tissues possess GH receptors, which, upon activation, can lead to IGF-I production within the tissues themáselves. IGF-I is considered a potent hormone capable of playing a key role in promoting growth, suggesting it mediates many growth and anabolic effects of growth hormone. It is hypothesized to foster cell growth and proliferation, as well as tissue and organ enlargement and strengthening, possibly aiding in protein synthesis and cell expansion. Preliminary exposure to CJC-1295 DAC in experimental models has been suggested to significantly affect average growth hormone levels, with studies reporting apparent 2 to 10-fold increases over 6 days or possibly longer. Additionally, it has been suggested that CJC-1295 DAC leads to dose-dependent increases in average IGF-I levels of 1.5 to 3-fold over approximately 9–11 days, with suggestions that IGF-I levels may remain high for at least two weeks in experimental models. Following repeated exposure to CJC-1295 DAC, average IGF-I levels appear to remain elevated above baseline for up to 28 days. In particular, data suggests a cumulative effect following repeated exposure to the compound.(5)

In 2006, another group of scientists evaluated GH pulsatility after a single occurrence of CJC-1295 DAC. They discovered that there appeared to be an approximately 50% increase in mean GH secretion and IGF-I levels after a single presentation of CJC-1295 DAC.(6) Researchers have suggested that the peptide could contribute to an increase in peak growth hormone levels of up to 7.5 times in the models studied.(6) It seemás that CJC-1295 DAC may interact with certain binding sites on the Growth Hormone-Releasing Hormone (GHRH) receptor protein. This interaction may lead to changes in the receptor's structure, potentially triggering a series of molecular processes. This interaction is believed to stimulate specific intracellular signaling proteins, often referred to as G-proteins.(7) Upon activation, these proteins can promote the production of secondary messengers, such as cyclic adenosine monophosphate (cAMP) or inositol triphosphate (IP3), which are considered to play crucial roles in cellular signaling pathways.(8) It is thought that secondary messengers, including cAMP, activate protein kinases, which are enzymes considered capable of modifying specific proteins. These kinases are considered capable of regulating cellular functions by phosphorylating transcription regulators, the proteins responsible for controlling gene expression. Once phosphorylated, it is speculated that these transcription regulators move into the nucleus of somatotroph cells, where they could influence genes involved in growth hormone production. This intricate cascade of events highlights the potential of CJC-1295 DAC to modulate growth hormone levels through a complex network of molecular interactions.

Additional animal studies were conducted to evaluate the potential of CJC-1295 DAC. One study evaluated murine models presented with the peptide or a placebo. Researchers concluded that exposing murine models daily to CJC-1295 DAC could fully normalize growth. Another finding was that CJC-1295 DAC presented every 2 or 3 days appeared to produce intermediate results, indicating a probable interval-dependent action.(9) Furthermore, this study suggests that CJC-1295 DAC could potentially impact body composition, apparently increasing muscle tissue hypertrophy without impacting, or even possibly reducing, fat tissue levels. Murine models in this study appeared to have a GHRH gene deletion (referred to as GHRHKO); observations suggested that CJC-1295 DAC can increase GH synthesis, leading to a beneficial alteration in body composition. Exposure to CJC-1295 DAC in these GHRHKO murine models appeared to preserve normal lean mass levels, unlike models that were not exposed and exhibited suboptimal lean mass levels. Furthermore, the amount of subcutaneous fat mass remained consistent with control levels in all peptide-associated groups, while GHRHKO murine models without CJC-1295 DAC exposure exhibited signs of increased fat levels. This indicates that CJC-1295 DAC could positively affect muscle and bone structure without promoting an increase in fat accumulation. Additionally, the study noted a possible increase in pituitary RNA and GH mRNA levels following exposure to CJC-1295 DAC, suggesting an enhanced presence of somatotroph cells, those believed to produce growth hormone in the pituitary gland. The authors commented that "CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that somatotroph proliferation had occurred, as confirmed by immunohistochemistry images.”(9)

Half Life of CJC-1295 DAC Peptide

In its original form, CJC-1295 DAC uses a technology called Drug Affinity Complex (DAC).(1) Unlike GHRH, which is considered to have a half-life of approximately 7 minutes, researchers report that CJC-1295 without DAC exhibits a longer half-life of 30 minutes due to its truncated 29-amino acid fragment, and 4 of the original amino acids in this fragment are replaced. Alterations in the peptide structure, specifically at amino acid positions 2, 8, 15, and 27, are believed to potentially improve the peptide's stability against breakdown by the enzyme dipeptidyl peptidase-4. These alterations are detailed below:

• At the 2nd position, L-alanine is substituted by D-alanine, a change believed to reinforce resistance against enzymatic degradation.
• At the 8th position, asparagine is replaced with glutamine, a modification that could reduce the risk of asparagine rearrangement and amide hydrolysis.
• The substitution of glycine with alanine at the 15th position is theorized to improve the peptide's bioactivity.
• The alteration of methionine to leucine at the 27th position is considered to potentially prevent methionine oxidation.

These modifications aim to improve the peptide's resistance and functional efficacy by mitigating enzymatic degradation and improving stability under physiological conditions. Furthermore, the peptide's half-life appears to be additionally extended to 6-8 days due to DAC technology.(10)

Auxiliary Studies of CJC-1295 DAC Peptide

In 2005, a clinical study aimed to evaluate the mechanism of action of CJC-1295 DAC in immunodeficiency virus (HIV) models associated with visceral obesity. In this study, models would be presented with CJC-1295 DAC for 3 months, followed by a 6-week follow-up period. However, this study was terminated during recruitment and no related results were published.(11)

According to a Norwegian study from 2009, a compound was presented for analysis to evaluate whether it contained prohibited substances or not. Researchers from the Norwegian Doping Control Laboratory and the School of Pharmacy reported that this substance was CJC-1295 DAC. In their published article, they concluded that "CJC-1295DAC is a releasing factor for growth hormone".(1)

The CJC-1295 DAC peptide is available only for research and laboratory purposes.

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).