CJC-1295 + Ipamorelin Blend

Researchers suggest that both CJC-1295 and Ipamorelin peptides increase growth hormone levels through potential triggering of the anterior pituitary gland. Scientists consider that once triggered, growth hormones can be naturally secreted, maintaining growth hormone levels in the organism.(3)

CJC-1295 peptide is a tetrasubstituted version of GHRH 1-29, developed to represent the shortest functional sequence of GHRH. GHRH 1-29 consists of the first 29 amino acids of the native GHRH peptide, and can potentially stimulate growth hormone production in the pituitary gland cells, called somatotropes. The peptide has four amino acid substitutions in its structure, which scientists suggest may improve its activity and resistance towards proteolytic enzymes. More specifically, the replaced amino acids appear to be the 2nd, 8th, 15th, and 27th amino acid. Due to these substitutions, the peptide might covalently bind to blood albumin, with trace amounts possibly capable of binding to fibrinogen and immunoglobulin G (IgG). As a result, the apparent half-life of the peptide may increase from 10 minutes to 30 minutes.(4) This may lead to elevated levels of plasma growth hormone and insulin-like growth factor 1 (IGF-1).

CJC-1295 might also be linked with the alleged Drug Affinity Complex (DAC) element, which can bind to plasma proteins. In particular, the DAC element in CJC-1295 alludes to the connection of the lysine N-epsilon-3-maleimidopropionamide derivative at the C-terminal end. By fusing the tetrasubstituted amino acid chain and the DAC element, CJC-1295 appears to show improved pharmacokinetics but retains comparable attraction to GHRH receptors in the pituitary gland, similar to natural GHRH.(5) More specifically, researchers comment that when the peptide was "selected for further pharmacokinetic evaluation, where it was found to be present in plasma beyond 72 h".

Ipamorelin is a man-made pentapeptide, also known as NNC 26-0161, which is believed to associate with a specific receptor on pituitary gland cells, termed the growth hormone secretagogue receptor (GHS-R1a). These receptors are considered to be located in the hypothalamus. Furthermore, GHS-R1a is often referred to as ghrelin receptors because ghrelin appears to be its main natural ligand. Ipamorelin seems to stand out from other GHSs as a potentially more selective compound, which may possibly stimulate the release of GH levels by somatotrope cells without also increasing other hormones produced by the anterior pituitary gland, such as prolactin.

When the peptide blend, sometimes also called a peptide stack, is presented in combination, research studies typically report that Ipamorelin exerts an initial action, exhibiting some sign of impact within the first two hours of presentation, and as it begins to decline, the CJC-1295 peptide may gradually complement the action.(6)

Chemical Composition

• Molecular Formula:
  CJC-1295: C152H252N44O42
  Ipamorelin: C38H49N9O5
• Molecular Weight:
  CJC-1295: 3367.9 g/mol
  Ipamorelin: 711.8 g/mol
• Other Known Titles:
  CJC-1295: CJC-1295 NO DAC; Mod GRF 1-29
  Ipamorelin: NNC 26-0161

CJC-1295 and Ipamorelin Blend and Half-Life Determination

Clinical studies have been conducted on test subjects to determine the half-life and individual pharmacokinetic profiles of the two peptides. In a study from the late 1990s,(6) a clinical trial was conducted on eight male test subjects with a concentration escalation design. The level of growth hormones was monitored after each instance of peptide presentation. At the end of the study, researchers suggested that there was a single episode of growth hormone release with the highest peak at 0.67 hours, after which there was an exponential decline to negligible concentrations of the compound. This study concluded that the Ipamorelin peptide appeared to exhibit a short half-life of 2 hours, after which the potential action seems to start diminishing.

CJC-1295, in contrast, appears to have a much longer half-life. Researchers comment that a single introduction of the peptide may upregulate growth hormone production by somatotropes for extended periods of time, thus apparently contributing "to an overall increase in [growth hormone] secretion … by 46%" and also potentially upregulating its main anabolic mediator insulin-like growth factor-1 (IGF-1) by 45% on average.(7) Another publication also observes that CJC-1295 may potentially upregulate "[growth hormone] concentrations by 2 to 10-fold," and estimates the peptide's half-life to range between 5.8 and 8.1 days.(8)

In this study from the early 2000s,(7) a clinical trial was conducted on male test subjects between 20 and 40 years old. The test subjects were divided into two groups; one group was presented with the placebo and the other with the peptide. Blood samples were taken from the subjects one week before and after the presentation of the CJC-1295 peptide (and placebo) to monitor growth hormone pulsatility levels. At the end of the study, it was suggested that CJC-1295 contributed to a 7.5-fold increase in growth hormone pulsatility levels compared to that of the placebo. In addition to apparently affecting growth hormone synthesis, scientists also suggest that CJC-1295 may interact with the survival and proliferation of the cells that synthesize it: the somatotrope cells in the anterior pituitary gland.(9) In a study on murine models, authors commented that "CJC-1295 caused an increase in total pituitary RNA and GH mRNA, suggesting that somatotrope proliferation had occurred, as confirmed by immunohistochemistry images".

To exert these apparent effects, CJC-1295 appears to interact with specific binding sites on the GHRH receptor protein, leading to conformational changes in the receptor structure and potentially initiating a cascade of molecular events. The binding appears to activate intracellular signaling proteins that potentially act as molecular switches.(10) These proteins are often termed G proteins, which, when activated, could drive the generation of secondary messengers such as cyclic adenosine monophosphate (cAMP) or inositol triphosphate (IP3).(11) Secondary messengers like cAMP may set in motion protein kinases, enzymes believed to alter distinct proteins. These kinases possess a modulatory capacity for cellular activities and may phosphorylate transcription regulators or proteins that oversee gene modulation. Once phosphorylated, these transcription regulators could migrate to the nucleus of somatotrope cells, possibly impacting genes associated with growth hormone formation.(7)

On the other hand, Ipamorelin appears to interact with anterior pituitary gland cells through the N-terminus of GHS-R1a, which has binding sites that seem to recognize specific sequences in the secretagogue. When Ipamorelin encounters this receptor, it may bind in a non-permanent manner through forces like hydrogen bonds and inter-molecular forces called van der Waals forces. This binding could cause the receptor to change its shape, potentially initiating cellular signals, mainly those involving G proteins. GHS-R1a could work with a specific part of G proteins called Gαq/11.(12) A main process initiated by GHS-R1a involves an enzyme called phospholipase C (PLC). Gαq/11 interacts with PLC, which can split a fat-like molecule, phosphatidylinositol 4,5-bisphosphate (PIP2), into two messenger molecules: IP3 (Inositol triphosphate) and DAG (Diacylglycerol). IP3 appears to bind to places in a cellular part called the endoplasmic reticulum, causing the release of calcium ions (Ca2+). Additionally, DAG could activate an enzyme called protein kinase C (PKC), which can add phosphate groups to other signaling molecules. All these steps could end with the "activation" of proteins that help release growth hormone from certain cells in the pituitary gland.(13)

The apparent synergistic action of CJC-1295 and Ipamorelin on growth hormone production by somatotrope cells in the anterior pituitary gland seems to result in a positive nitrogen balance and a potential increase in lean mass in test models. In a particular study, researchers sought to test the metabolic capabilities of Ipamorelin within the context of certain liver markers related to alpha-amino-nitrogen processing during artificially provoked catabolism. The team evaluated the liver's ability to produce urea-N (CUNS), a potential metric of nitrogen processing within the liver. They examined observable levels of messenger RNA (mRNA) linked to urea cycle enzymes in the liver, measured the overall nitrogen balance, and postulated nitrogen quantities in different organs. It was proposed that Ipamorelin might have led to a 20% decrease in CUNS, in contrast to the catabolic condition that was artificially provoked by the researchers. Furthermore, it could possibly have decreased the manifestation of urea cycle enzymes, restored nitrogen balance, and theoretically adjusted or improved nitrogen values in organs.(14)