CJC-1295 (With DAC)

Peptide Information

CJC1295 With DAC Research

What is the research background of CJC1295 With DAC?

The application of traditional growth hormone-releasing hormone (GHRH) in treatment is limited by its short duration of action. This has prompted researchers to seek more long-acting growth hormone-releasing hormone analogs to improve treatment efficacy and convenience. With people's pursuit of health and beauty, public online folk pharmacology has provided the impetus for shortcuts to achieve muscle enhancement, fat reduction, and youthful skin. Against this backdrop, synthetic growth hormone analogs such as CJC1295 With DAC have attracted attention. Research shows that forum users demonstrate proficiency and experience in its multi-purpose use, and the purposes for choosing to use such substances include weight loss, muscle enhancement, skin rejuvenation, improved sleep, and wound healing, etc^[1]. As a long-acting growth hormone-releasing hormone analog, the development of CJC1295 With DAC is based on an in-depth understanding of the regulatory mechanism of growth hormone. Although most children with isolated growth hormone (GH) deficiency have a good growth response to GHRH, the half-life of GHRH is extremely short, limiting its therapeutic effect. To address this issue, researchers have developed CJC1295 With DAC, a long-acting GHRH analog. Studies have shown that it incorporates a functional maleimide group at the C-terminus, allowing it to covalently bind to plasma proteins such as serum albumin, thereby increasing its half-life and being able to stimulate growth hormone production in humans for more than six days after a single administration ^[2]

What is the mechanism of action of CJC1295 With DAC in the treatment of specific diseases?

Stimulating growth hormone release: 

CJC1295 With DAC is a peptide-based drug that can stimulate the production of growth hormone (GH) from the pituitary gland ^{[2, 3]} It incorporates a functional maleimide group at the C-terminus, allowing it to covalently bind to plasma proteins such as serum albumin. This binding gives the CJC1295-protein conjugate a much longer half-life and enables it to stimulate GH production in humans for more than six days after a single administration. Studies have shown that subcutaneous injection of CJC1295 With DAC can lead to a sustained, dose-dependent increase in the levels of GH and insulin-like growth factor I (IGF-I) in healthy adults ^{[2, 3]} After a single injection of CJC1295 With DAC, the average plasma GH concentration increased by 2-10 times and lasted for 6 days or longer, and the average plasma IGF-I concentration increased by 1.5-3 times and lasted for 9-11 days. The estimated half-life of CJC1295 With DAC is 5.8-8.1 days. After multiple administrations, the average IGF-I level remained above the baseline level for up to 28 days.

The role in growth hormone deficiency: 

In animal models with growth hormone (GH) deficiency, CJC1295 With DAC has shown positive effects. For mice with GHRH gene ablation, animals receiving a daily dose of CJC1295 With DAC showed normal body weight and body length^[4] Mice treated every 48 and 72 hours had higher body weight and body length than placebo-treated animals. Although complete normalization of growth was not achieved, some improvement was also demonstrated. In all treatment groups, the relative lean mass and subcutaneous fat mass were normal. CJC1295 With DAC also caused an increase in total pituitary RNA and GH mRNA, indicating the growth of somatotroph cells, a result confirmed by immunohistochemical images.

How does CJC1295 With DAC achieve a more sustained effect in terms of structure?

Covalent binding with serum albumin: 

CJC-1295 incorporates a functional maleimide group at the C-terminus, which allows the substance to covalently bind to plasma proteins such as serum albumin ^[2] This conjugation enables CJC-1295 to remain active in the blood, and its duration of action is significantly longer than that of non-conjugated peptide drugs that are rapidly excreted. Once bound to serum albumin, CJC-1295 forms a relatively stable complex, thus prolonging its duration of action in the body. For example, when the maleimide group of CJC-1295 covalently binds to the free throat on serum albumin, its half-life in the blood is greatly increased. This conjugation method is unique among performance-enhancing peptides and lays the foundation for the sustained effect of CJC-1295 ^[5].

Improving stability: 

Three maleimide derivatives were synthesized by modifying the human growth hormone-releasing factor(hGRF), among which CJC-1295 is a tetra-substituted form of hGRF (1-29), with the Nε-3-maleimidopropionamide derivative of lysine added at the C-terminus ^[6].This structure makes CJC-1295 have enhanced in vitro stability against dipeptidyl peptidase-IV. In the growth hormone secretion analysis of cultured rat anterior pituitary cells, all three human serum albumin conjugates were biologically active. When the maleimide derivatives were subcutaneously injected alone into normal male Sprague Dawley rats, acute growth hormone secretion was detected in the plasma. Among them, CJC-1295 showed a 4-fold increase in the area under the growth hormone curve compared with hGRF (1-29) within 2 hours. In addition, Western blot analysis of the plasma of rats injected with CJC-1295 showed the presence of CJC-1295 immunoreactive substance in the band corresponding to serum albumin, which appeared 15 minutes after injection and persisted in the circulation for more than 24 hours. These results indicate that CJC-1295 is a stable and active hGRF (1-29) analog with an extended plasma half-life ^[6].

Effect of CJC-1295 on total body wt (TBW; means±SE). At the end of the 5-wk treatment period, the CJC/24 h group exhibited completely normal TBW. CJC/48 h and CJC/72 h groups reached a significantly higher TBW compared with the GHRHKO/pbo group, although it remained smaller than in the HTZ/pbo group.

Source:PubMed^[4]

What are the clinical applications of CJC1295 With DAC?

CJC1295 With DAC can effectively stimulate the secretion of growth hormone (GH). Multiple studies have shown that this drug can increase the average plasma GH concentration in healthy adults in a dose-dependent manner ^[3]. For example, in a study of healthy subjects, subjects aged between 21 and 61 years old had an average plasma GH concentration increase of 2-10 times for 6 days or longer after receiving subcutaneous injection of CJC1295 With DAC. This effect of stimulating growth hormone secretion is of great significance for patients with growth hormone deficiency.

For children with growth hormone deficiency, although most children have a good growth response to growth hormone-releasing hormone (GHRH), the short half-life of GHRH limits its clinical application. As a long-acting GHRH analog, CJC1295 With DAC can selectively covalently bind to endogenous albumin, thus prolonging its half-life and duration of action. In the study of GHRH gene knockout (GHRHKO) mice, it was found that once-daily administration of CJC1295 With DAC can maintain the normal body weight and body length of mice, indicating that this drug has potential application value in the treatment of childhood growth hormone deficiency^[4] .

CJC1295 With DAC can not only stimulate growth hormone secretion but also increase the level of insulin-like growth factor I. In clinical studies, after a single injection of CJC1295 With DAC, the average plasma IGF-I concentration in healthy adults increased by 1.5-3 times within 9-11 days. And after multiple administrations, the average IGF-I level can remain above the baseline for up to 28 days ^[4]. IGF-I has a variety of important physiological functions in the human body, including promoting cell proliferation, differentiation, and survival, and regulating metabolism, etc. Therefore, increasing the level of IGF-I may have a positive effect on the treatment of various diseases.

What are the potential applications of CJC1295 With DAC in clinical and related fields?

Growth hormone deficiency: 

CJC1295 With DAC can continuously stimulate the pituitary gland to secrete growth hormone. For patients with insufficient growth hormone secretion due to various reasons, especially children and adolescents, it can effectively improve the condition of growth and development retardation and promote height growth. In the treatment of growth hormone deficiency, traditional growth hormone replacement therapy has achieved certain results, but CJC1295 With DAC has unique advantages. It can covalently bind to endogenous albumin, thus prolonging its half-life and duration of action^[4]. For example, in the study of GHRH gene knockout mice, it was found that the daily administration of CJC-1295 treatment can maintain the normal body composition and growth of GHRHKO mice, including normal body weight, body length, relative lean mass, and subcutaneous fat mass, and at the same time can also cause an increase in total pituitary RNA and GH mRNA, confirming the proliferation of growth hormone-secreting cells (Alba M, 2006).

For adult patients with growth hormone deficiency, CJC1295 With DAC can not only improve body composition, increase muscle mass, and reduce body fat but also improve the quality of life. Growth hormone also plays an important role in the adult body. It is involved in the metabolic regulation of proteins, fats, and carbohydrates. The lack of growth hormone will lead to problems such as increased body fat, decreased muscle mass, and reduced bone density. The use of CJC1295 With DAC can correct these abnormalities to a certain extent and improve the physical condition of patients.

Anti-aging: 

With the increase of age, the secretion of human growth hormone gradually decreases, which will trigger a series of aging-related changes. CJC1295 With DAC has potential application value in anti-aging. It can increase the secretion of growth hormone to a certain extent, which is helpful to improve the decline of physical functions related to aging. For example, it can increase bone density. Growth hormone can promote the activity of osteoblasts, increase bone mass, and prevent osteoporosis; enhance muscle strength. Growth hormone can stimulate muscle protein synthesis, increase muscle mass and strength; improve skin elasticity and luster. Growth hormone may make the skin more firm and elastic by promoting collagen synthesis^[4].

Sports medicine and rehabilitation: 

CJC1295 With DAC has potential applications in the rehabilitation of sports injuries and the improvement of athletic performance. It can promote muscle repair and regeneration and accelerate wound healing. When an athlete is injured, the body needs to repair the damaged tissue as soon as possible to restore athletic ability. Growth hormone plays an important role in this process. It can stimulate cell proliferation and differentiation, promote protein synthesis, and accelerate the repair of muscles and other tissues^[4]. At the same time, CJC1295 With DAC may increase muscle strength and endurance and enhance athletic ability. Growth hormone can increase muscle mass and improve the contractile ability of muscles, thereby enhancing the strength and endurance of athletes^[4] .

Metabolic diseases: 

For some metabolic diseases such as obesity and insulin resistance, CJC1295 With DAC may affect energy metabolism and fat distribution and improve insulin sensitivity by regulating the growth hormone-insulin-like growth factor axis. Obesity is a common metabolic disease, and its occurrence is related to the imbalance between energy intake and consumption. Growth hormone can promote fat breakdown and increase energy consumption, thus helping to control body weight. Insulin resistance refers to the decrease in the body's sensitivity to insulin, leading to an increase in blood sugar levels. Growth hormone can improve insulin sensitivity and reduce blood sugar levels^[4].

In conclusion, CJC1295 With DAC has shown positive effects in multiple aspects in the field of growth hormone regulation. It has important value not only in the treatment of growth hormone deficiency but also in sports medicine and rehabilitation and anti-aging research. Its long-acting mechanism of action reduces the frequency of administration, and its good safety and tolerability also provide strong support for its clinical application. Although it is still in the research stage in some fields such as anti-aging, the effects already demonstrated are sufficient to prove its unique advantages and broad application prospects in the field of life sciences and related fields.

Relevant Citations

[1] Van Hout M C, Hearne E. Netnography of Female Use of the Synthetic Growth Hormone CJC-1295: Pulses and Potions[J]. Substance Use & Misuse, 2016,51(1):73-84.DOI:10.3109/10826084.2015.1082595.

[2] Timms M, Ganio K, Steel R. A method for confirming CJC-1295 abuse in equine plasma samples by LC-MS/MS[J]. Drug Testing and Analysis, 2019,11(8):1248-1257.DOI:10.1002/dta.2599.

[3] Teichman S L, Neale A, Lawrence B, et al. 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]. Journal of Clinical Endocrinology & Metabolism, 2006,91(3):799-805.DOI:10.1210/jc.2005-1536.

[4] Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse[J]. American Journal of Physiology-Endocrinology and Metabolism, 2006,291(6):E1290-E1294.DOI:10.1152/ajpendo.00201.2006.

[5] Timms M, Ganio K, Forbes G, et al. An immuno polymerase chain reaction screen for the detection of CJC-1295 and other growth-hormone-releasing hormone analogs in equine plasma[J]. Drug Testing and Analysis, 2019,11(6):804-812.DOI:10.1002/dta.2554.

[6] Jetté L, Léger R, Thibaudeau K, et al. 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[J]. Endocrinology, 2005,146(7):3052-3058.DOI:10.1210/en.2004-1286.