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Cjc-1295 Structure And Mechanism — Common Mistakes

By Editorial Desk · published 2026-04-21 · last reviewed 2026-05-10 · Blog

A practical reference on DAC linker: what it is, how it behaves, what the literature reports, and where the honest uncertainties sit.

Reviewed 2026-05-10. Anything still debated is marked as such rather than presented as settled.

CJC-1295 Structure And Mechanism

The drug affinity complex is a maleimidopropionic acid group attached to a lysine side chain. It reacts with the free thiol of cysteine-34 on circulating albumin, forming a covalent bond. This conjugation keeps the peptide in the bloodstream and shields it from rapid renal filtration and proteolysis. Reported circulation half-lives for the albumin-bound form fall in the range of roughly six to nine days in early human studies.

Binding to GHRH receptors on pituitary somatotroph cells triggers cyclic AMP signaling and stimulates growth hormone synthesis and release. Because the peptide acts upstream of the pituitary, effects are mediated through endogenous growth hormone rather than direct receptor activation in peripheral tissues. Increases in insulin-like growth factor 1 are generally described as a downstream consequence. Most published human exposure data come from small early-stage studies, and the clinical significance of the pharmacokinetic profile remains incompletely characterized.

CJC-1295 is a synthetic analogue of growth hormone-releasing hormone, built on the 29-amino-acid GHRH(1-29) fragment. Four substitutions distinguish it from the natural sequence: D-alanine at position 2, glutamine at position 8, alanine at position 15, and leucine at position 27. These changes reduce enzymatic cleavage and extend the peptide's persistence in circulation. The compound is discussed in two forms, one carrying a drug affinity complex and one without it.

Mechanism and Pharmacokinetics

Binding of the peptide to the growth hormone-releasing hormone receptor on pituitary somatotrophs triggers a G protein coupled cascade that raises cyclic AMP and opens calcium channels. The result is greater secretion of growth hormone into the bloodstream. Because the peptide acts at the same receptor as the natural hypothalamic hormone, its effect is amplified pulse size rather than an entirely separate release pathway. Receptor binding alone does not determine the response, since somatostatin tone and other inputs modulate the final output.

The albumin-binding version stays in circulation for days, because covalent attachment to serum albumin shields the peptide from rapid filtration and degradation. Reported half-lives for this form fall in the range of several days. The version without the linker is cleared in minutes, with estimates often near thirty minutes in animal work. These figures come from small studies and vary with assay method, species, and route, so they are best read as approximate rather than fixed constants.

Cjc-1295 at a glance

PropertyValueNotes
Physical formLyophilized white powderSupplied as a freeze-dried solid for research use
Molecular weightApproximately 3,647 Da (DAC form)Lower for the variant lacking the albumin-binding moiety
SolubilitySoluble in water and aqueous bufferTypically dissolved in sterile or bacteriostatic water
Typical storage temperature−20 °C or belowDry powder, desiccated and protected from light
Common analytical methodReversed-phase HPLC with mass spectrometryUsed for purity estimation and identity confirmation

Receptor Action and Pharmacokinetics

CJC-1295 acts at the growth hormone-releasing hormone receptor, a G-protein-coupled receptor found on somatotroph cells in the anterior pituitary. Binding triggers a rise in cyclic AMP and calcium entry, which promotes release of stored growth hormone. Because the peptide mimics the body's own releasing hormone, it amplifies existing secretory pulses rather than driving continuous output. The size of the response therefore depends partly on the subject's own hormonal rhythm and feedback state.

The attached maleimide group explains the unusual duration of the DAC version. After injection it reacts with the thiol of cysteine-34 on serum albumin, forming a stable covalent bond. The resulting conjugate is too large for rapid kidney filtration and is shielded from many peptidases. Reported half-lives for this form reach several days, whereas the version without the group is cleared in roughly half an hour. That gap is the main pharmacological difference between the two.

Downstream of growth hormone, the liver and other tissues increase production of insulin-like growth factor 1, a mediator of many growth-promoting effects. Studies have documented elevated levels of both hormones after dosing, and the rise from the long-acting form persists longer than that produced by shorter-acting analogues. What remains unclear is whether sustained elevation of these markers translates into meaningful clinical benefit, and whether prolonged exposure carries risks that short trials could not detect.

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Molecular Background and Naming

CJC-1295 is a synthetic peptide designed as a long-acting analogue of growth hormone-releasing hormone (GHRH). Its structure derives from the first 29 amino acids of native GHRH, a fragment often called GRF(1-29). Four substitutions were introduced to slow enzymatic breakdown and extend activity relative to the natural sequence. The compound was developed by ConjuChem as part of a broader effort to improve the pharmacokinetic profile of peptide hormones. It is studied in laboratory and clinical research settings rather than appearing as a naturally occurring substance.

Two related forms circulate in technical discussion under the same family name. The original version carries a drug affinity complex (DAC) that binds covalently to serum albumin after administration, and this linkage substantially extends circulation time. A second form, frequently written as modified GRF(1-29) or CJC-1295 without DAC, lacks that linker and clears much faster. The naming is a frequent source of confusion because the shorthand CJC-1295 can refer to either form depending on the source. Reports sometimes fail to specify which variant was studied.

Structure And Receptor Pharmacology

Two related forms appear under the CJC-1295 name. The simpler analogue, commonly written as modified GRF(1-29), carries the four substitutions but no additional conjugation. The second form attaches a maleimidopropionic acid linker to a lysine residue, a modification frequently called the drug affinity complex. That linker reacts with the free thiol on serum albumin to form a covalent bond. Because albumin has a long residence time in blood, the conjugated peptide stays in circulation far longer than the unconjugated analogue.

Receptor level activity follows the canonical GHRH pathway. The peptide binds the GHRH receptor, a class B G protein coupled receptor on somatotroph cells of the anterior pituitary. Binding raises intracellular cyclic AMP, which promotes calcium entry and the release of growth hormone into the bloodstream. Because the molecule acts at the same receptor as the endogenous hormone, its effect is superimposed on the natural pulsatile rhythm rather than replacing it. Whether sustained receptor occupation leads to desensitization is not fully settled.

Further detail

== Safety == Cyanuric acid is classified as "essentially nontoxic". The 50% oral median lethal dose (LD50) is 7700 mg/kg in rats. However, when cyanuric acid is present together with melamine (which by itself is another low-toxicity substance), it will form an insoluble and rather nephrotoxic complex, as evidenced in dogs and cats during the 2007 pet food contamination and in children during the 2008 Chinese milk scandal cases.

Several efforts to develop standards in the NGS field have been attempted to address these challenges, most of which have been small-scale efforts arising from individual labs. Most recently, a large, organized, FDA-funded effort has culminated in the BioCompute standard. On 26 October 1990, Roger Tsien, Pepi Ross, Margaret Fahnestock and Allan J Johnston filed a patent describing stepwise ("base-by-base") sequencing with removable 3' blockers on DNA arrays (blots and single DNA molecules). In 1996, Pål Nyrén and his student Mostafa Ronaghi at the Royal Institute of Technology in Stockholm published their method of pyrosequencing. On 1 April 1997, Pascal Mayer and Laurent Farinelli submitted patents describing DNA colony sequencing. The DNA sample preparation and random surface-polymerase chain reaction (PCR) arraying methods described in this patent, coupled to Roger Tsien et al.'s "base-by-base" sequencing method, is now implemented in Illumina's Hi-Seq genome sequencers. In 1998, Phil Green and Brent Ewing of the University of Washington described their phred quality score for sequencer data analysis, a landmark analysis technique that gained widespread adoption, and which is still the most common metric for assessing the accuracy of a sequencing platform. Lynx Therapeutics published and marketed massively parallel signature sequencing (MPSS), in 2000.

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Sources: en.wikipedia.org

Supporting material

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The 62-ton Ivy Mike device built by the United States and exploded on 1 November 1952, was the first fully successful hydrogen bomb (thermonuclear bomb). In this context, it was the first bomb in which most of the energy released came from nuclear reaction stages that followed the primary nuclear fission stage of the atomic bomb. The Ivy Mike bomb was a factory-like building, rather than a deliverable weapon. At its center, a very large cylindrical, insulated vacuum flask or cryostat, held cryogenic liquid deuterium in a volume of about 1000 liters (160 kilograms in mass, if this volume had been completely filled). Then, a conventional atomic bomb (the "primary") at one end of the bomb was used to create the conditions of extreme temperature and pressure that were needed to set off the thermonuclear reaction. Within a few years, so-called "dry" hydrogen bombs were developed that did not need cryogenic hydrogen. Released information suggests that all thermonuclear weapons built since then contain chemical compounds of deuterium and lithium in their secondary stages. The material that contains the deuterium is mostly lithium deuteride, with the lithium consisting of the isotope lithium-6. When the lithium-6 is bombarded with fast neutrons from the atomic bomb, tritium (hydrogen-3) is produced, and then the deuterium and the tritium quickly engage in thermonuclear fusion, releasing abundant energy, helium-4, and even more free neutrons. "Pure" fusion weapons such as the Tsar Bomba are believed to be obsolete.

State and local programs are not permitted to participate. The failure to share data has caused foreign governments to refuse donations of expired medications. One exception occurred during the 2010 Swine Flu Epidemic when the FDA authorized expired Tamiflu based on SLEP Data. The SLEP discovered that drugs such as Cipro remained effective nine years after their shelf life, and, as a cost-saving measure, the US military routinely uses a wide range of SLEP tested products past their official shelf life if drugs have been stored properly.

Sources: en.wikipedia.org

Frequently asked questions

How does CJC-1295 differ from modified GRF(1-29)?

The two share the same 29-amino-acid backbone. CJC-1295 carries an additional albumin-binding moiety that markedly extends its residence time in circulation, while the form without that moiety clears faster. Literature sometimes applies the name loosely to either variant.

Is CJC-1295 an approved medicine?

It has not been approved by major regulatory agencies for any therapeutic indication. Material sold under this name is typically distributed for laboratory research only. Clinical use is not supported by large controlled trials.

What is known about its half-life?

Early human studies of the albumin-binding form reported circulation half-lives on the order of several days. The value depends on assay method and study design. Estimates for the form without the binding moiety are considerably shorter.

How long does the albumin-binding form remain active?

Reported values cluster in the range of several days, reflecting slow release from the albumin complex. Estimates differ across species and assay platforms. The figure describes circulation time in study settings rather than a fixed property.

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