CJC-1295 DAC (5mg)

Description

CJC-1295 DAC Peptide

CJC-1295 DAC is a synthetic analog of growth hormone-releasing hormone (GHRH) that has the potential to enhance plasma levels of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).[1] Drug affinity complex (DAC) is an additive component that is considered to prolong the half-life of CJC-1295. Researchers have created several synthetic modifications of growth hormone-releasing hormone (GHRH), which appear to retain certain selective traits of the hormone while eliminating others. CJC-1295 is one such synthetic analog, comprising the first 29 amino acids of GHRH. This is believed to lend secretagogue characteristics with greater solubility, which may be easier to synthesize in larger volumes.

CJC-1295 DAC shares similarities with other GHRH analogs like Sermorelin, as both are derivatives of the first 29 amino acids of GHRH. CJC-1295 is structurally identical to Modified GRF (1-29). In particular, CJC-1295 DAC and Mod GRF (1-29) exhibit four alterations within their 29 amino acid sequence, specifically at the 2nd, 8th, 15th, and 27th positions. These modifications are hypothesized to enhance the peptides’ resistance to enzymatic breakdown, particularly by dipeptidyl peptidase-4 (DPP-4). For instance, the replacement of L-alanine with D-alanine at the 2nd position may contribute to increased resistance to molecular degradation. Substituting asparagine with glutamine at the 8th position may conceivably reduce the likelihood of asparagine rearrangement and amide hydrolysis. The substitution of glycine with alanine at the 15th position is suggested to enhance bioactivity. Finally, the alteration from methionine to leucine at the 27th position is thought to aid in mitigating the risk of methionine oxidation. The primary differential between the two peptides, CJC-1295 DAC and Mod GRF (1-29), is the addition of DAC to the CJC-1295 molecule. DAC is attached to CJC-1295 through a lysine linker to extend the peptide’s pharmacokinetics. DAC appears to facilitate the association of peptides with blood proteins such as albumin. This appears to enhance their half-life, as compared to similar peptides such as GRF (1-29).[2] This occurrence may be attributed to the purported ability of DAC to interact with plasma proteins. Specifically, it seems that the DAC element involves the association of a lysine derivative, N-epsilon-3-maleimidopropionamide, with the C-terminus of CJC-1295 DAC. The incorporation of this altered amino acid sequence into the DAC configuration may plausibly improve the pharmacokinetics of CJC-1295 DAC, potentially prolonging its half-life to around eight days.

Specifications

Other Known Titles: CJC-1295 with DAC

Molecular Formula: C152H252N44O42

Molecular Weight: 3367.954 g/mol

Sequence: H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys(Mal)-NH2

CJC-1295 DAC Research

CJC-1295 DAC and Pituitary Cell Receptors

Studies indicate that the peptide may enhance peak growth hormone levels up to seven and a half times in the models examined.[3] CJC-1295 DAC may interact with specific binding sites on the growth hormone-releasing hormone (GHRH) receptor. Such interactions might alter the receptor’s configuration, potentially initiating a cascade of molecular events. This binding is thought to activate particular intracellular signaling proteins, commonly known as G-proteins.[4] When these proteins are activated, they may facilitate the production of secondary messengers like cyclic adenosine monophosphate (cAMP) or inositol trisphosphate (IP3), which are considered to play essential roles in cellular signaling pathways.[5] These secondary messengers are believed to activate protein kinases, enzymes that alter specific proteins. These kinases may modify cellular functions by phosphorylating transcription regulators, which are proteins that control gene expression. Upon phosphorylation, these transcription regulators are hypothesized to enter the nucleus of somatotroph cells, potentially affecting the genes that govern growth hormone production. This sequence of events underscores the potential of CJC-1295 DAC to influence growth hormone levels through a detailed network of molecular interactions.

CJC-1295 DAC and Growth Hormone Release

The peptide was initially developed to trigger growth hormone release and is a synthetic analog of the naturally occurring GHRH. Murine model experiments have reported that a single exposure to the peptide may induce almost 2-10 times higher production of growth hormone as compared to control models.[6] GH expression appears to reach a maximum level after 2 hours of peptide introduction, and the action appears to be maintained up to six days later. The peptide appears to maintain the natural physiological level of growth hormone, unlike other secretagogues. In other words, CJC-1295 DAC may have the potential to perform as a physiological GHRH and maintain the natural biological high and low expression pattern in growth hormone levels. CJC-1295 DAC appears to maintain the physiological level of the hormone while enhancing its release in the blood. CJC-1295 DAC has been studied in relation to the physiological regulation of growth hormone in the course of protein synthesis, fat metabolism, blood sugar, hypertrophy, bone density, hyperplasia, and myocardial function. The production of growth hormone may interact with receptors on liver cells, potentially initiating a series of intracellular signaling events. This interaction may activate the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Following activation, STAT proteins may possibly translocate to the nucleus and bind to specific DNA sequences known as response elements, which might facilitate the transcription of the IGF-I gene. It has been posited that CJC-1295 DAC may lead to increases in average IGF-I levels, ranging from 1.5- to 3-fold over approximately 9–11 days, with indications that these elevated levels might persist for at least two weeks in experimental settings. After repeated exposure to CJC-1295 DAC, average IGF-I levels seem to sustain an elevation above the initial baseline for up to 28 days. Importantly, data suggests a cumulative action with repeated exposures to the compound.[6]

CJC-1295 DAC and Infertility

Studies from the early 1990s suggest that CJC-1295 DAC and other GRF analogs may exert stimulatory action in female infertility studies. Murine models of superovulation have suggested that growth hormone and IGF-1 levels increase in blood around the time of ovulation.[7] Thus, exposure to CJC-1295 DAC and GRF analogs may promote ovulation in female animals, possibly through the IGF-1 and growth hormone expression cycle. The exposure of growth hormone secretagogues like CJC-1295 DAC may be sufficient to promote ovulation. Scientists have further suggested these analogs may improve sperm production, though research is inconclusive.

CJC-1295 DAC and Growth

Research has suggested that CJC-1295 may restore the physiological release of growth hormone in murine models lacking normal growth hormone physiology.[8] Jette et al. notes that “CJC-1295, showed a 4-fold increase in GH area under the curve over a 2-h period.” The peptide may potentially be researched in the context of growth anomalies in different mammalian species. Maintenance of the circadian cycle of growth hormone release appears crucial to producing downstream hormones, such as insulin-like growth factor-1 (IGF-1). Further investigations have also indicated that exposure to CJC-1295 DAC in murine models may potentially stabilize growth patterns. These studies propose that CJC-1295 DAC may influence body composition, possibly by promoting muscle hypertrophy without affecting (perhaps even decreasing), fat tissue levels. Specifically, the murine models examined exhibited a genetic deletion of the GHRH gene (referred to as GHRHKO); findings imply that CJC-1295 DAC may enhance growth hormone production, resulting in favorable changes in body composition. In these GHRHKO murine models, exposure to CJC-1295 DAC seemed to maintain standard levels of lean mass, in contrast to models not exposed, which displayed lower than optimal lean mass. Moreover, the quantity of subcutaneous fat mass remained similar to that observed in the control groups associated with peptide exposure, while GHRHKO models not exposed to CJC-1295 DAC showed signs of increased fat mass. This suggests that CJC-1295 DAC may beneficially influence muscle and bone structure without contributing to fat gain. The study also observed a potential elevation in pituitary RNA and GH mRNA levels following exposure to CJC-1295 DAC, indicating a probable increase in the population of somatotroph cells—cells believed to synthesize growth hormone within the pituitary gland. The researchers posited that “CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that proliferation of somatotroph cells had occurred, as confirmed by immunohistochemistry images.”[1]

Disclaimer: The products mentioned are not intended for human or animal consumption. Research chemicals are intended solely for laboratory experimentation and/or in-vitro testing. Bodily introduction of any sort is strictly prohibited by law. All purchases are limited to licensed researchers and/or qualified professionals. All information shared in this article is for educational purposes only.

References

1. 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.
2. Gautam D, Jeon J, Starost MF, Han SJ, Hamdan FF, Cui Y, Parlow AF, Gavrilova O, Szalayova I, Mezey E, Wess J. Neuronal M3 muscarinic acetylcholine receptors are essential for somatotroph proliferation and normal somatic growth. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6398-403. doi: 10.1073/pnas.0900977106. Epub 2009 Mar 30. PMID: 19332789; PMCID: PMC2662962.
3. 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.
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. 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.
7. Guo S, Li Z, Yan L, Sun Y, Feng Y. GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity. Drug Des Devel Ther. 2018 Jun 7;12:1621-1631. doi: 10.2147/DDDT.S162541. PMID: 29922037; PMCID: PMC5995291.
8. 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.

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Dr. Usman

Dr. Usman (BSc, MBBS, MaRCP) completed his studies in medicine at the Royal College of Physicians, London. He is an avid researcher with more than 30 publications in internationally recognized peer-reviewed journals. Dr. Usman has worked as a researcher and a medical consultant for reputable pharmaceutical companies such as Johnson & Johnson and Sanofi.