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Cjc-1295 Structure And Mechanism — Research Overview

By Editorial Desk · published 2025-07-07 · last reviewed 2025-07-26 · Faq

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

This page was last updated on 2025-07-26 and is reviewed periodically as new material appears.

CJC-1295 Structure And Mechanism

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.

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.

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.

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

Molecular Background and Naming

The peptide backbone includes a D-alanine at position two, which resists cleavage by dipeptidyl peptidase IV, and several other substitutions that reduce degradation. Its molecular weight is roughly 3.4 kDa without the linker and about 3.6 kDa with it. The molecule is water soluble and is normally supplied as a lyophilized powder. Precise sequence and mass values depend on which variant is described, so technical documents usually state the exact form being referenced.

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.

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Receptor Action and Pharmacokinetics

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.

Mechanism and Pharmacokinetics

Studies in this area generally track growth hormone pulses, insulin-like growth factor 1 concentrations, and occasionally body composition endpoints. Most published human data come from early, small trials, and questions about long-term effects remain open. Whether repeated exposure alters pituitary responsiveness over time is not settled. Analytical work relies on immunoassays for the hormones and on mass spectrometry for the peptide itself, because the two measurements answer different questions.

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.

Reference notes

== Drug target and mechanism of action == Keratinocyte growth factor (KGF) resides in the family of fibroblast growth factor (FGF). The drug's target is the KGF receptor. Through the binding of this drug to the aforementioned receptor, Palifermin stimulates epithelial cell proliferation, differentiation, and upregulation of cytoprotective mechanisms to reduce the symptoms of oral mucositis.

Pharmacy informatics is the combination of pharmacy practice science and applied information science. Pharmacy informaticists work in many practice areas of pharmacy, however, they may also work in information technology departments or for healthcare information technology vendor companies. As a practice area and specialist domain, pharmacy informatics is growing quickly to meet the needs of major national and international patient information projects and health system interoperability goals. Pharmacists in this area are trained to participate in medication management system development, deployment, and optimization.

=== Subjects === Participants in phase I drug trials do not gain any direct health benefit from taking part. They are generally paid a fee for their time, with payments regulated and not related to any risk involved. Motivations of healthy volunteers is not limited to financial reward and may include other motivations such as contributing to science and others. In later phase trials, subjects may not be paid to ensure their motivation for participating with potential for a health benefit or contributing to medical knowledge. Small payments may be made for study-related expenses such as travel or as compensation for their time in providing follow-up information about their health after the trial treatment ends.

== History == The British have had a system of heroin maintenance since the 1920s. For decades it supplied a few hundred addicts nationwide, most of whom were doctors themselves. It was de-emphasized considerably during the 1960s-1980s as a result of the U.S.-led war on drugs. In the 1980s and early 1990s, Dr John Marks ran heroin-prescribing clinics in Liverpool, Widnes and Warrington that were highly controversial. Because of the lack of large-scale trials, only anecdotal evidence existed as to the efficacy of the treatment. This changed in 1994 when Switzerland, faced with one of the largest open drug scenes in Europe at the time, started large-scale trials on the potential use of diamorphine as a maintenance drug. They proved diamorphine to be a viable maintenance drug which has shown equal or better rates of success than methadone in terms of assisting long-term users establish stable, crime-free lives. These results encouraged countries like Germany and the Netherlands to conduct their own trials and finally to include heroin-assisted treatment fully as a part of the national health system in 2009. In Switzerland, heroin has been made available under supervision to addicts since around 1994. Several studies have been conducted between 1994 and 1996.

Sources: en.wikipedia.org

Notes from published material

=== Surgery === If the TIA affects an area that is supplied by the carotid arteries, a carotid ultrasound scan may demonstrate stenosis, or narrowing, of the carotid artery. For people with extra-cranial carotid stenosis, if 70-99% of the carotid artery is clogged, carotid endarterectomy can decrease the five-year risk of ischemic stroke by approximately half. For those with extra-cranial stenosis between 50 and 69%, carotid endarterectomy decreases the 5-year risk of ischemic stroke by about 16%. For those with extra-cranial stenosis less than 50%, carotid endarterectomy does not reduce stroke risk and may, in some cases, increase it. The effectiveness of carotid endarterectomy or carotid artery stenting in reducing stroke risk in people with intracranial carotid artery stenosis is unknown. In carotid endarterectomy, a surgeon makes an incision in the neck, opens up the carotid artery, and removes the plaque occluding the blood vessel. The artery may then be repaired by adding a graft from another vessel in the body or a woven patch. In patients who undergo carotid endarterectomy after a TIA or minor stroke, the 30-day risk of death or stroke is 7%. Carotid artery stenting is a less invasive alternative to carotid endarterectomy for people with extra-cranial carotid artery stenosis. In this procedure, the surgeon makes a small cut in the groin and threads a small flexible tube, called a catheter, into the patient's carotid artery. A balloon is inflated at the site of stenosis, opening up the clogged artery to allow for increased blood flow to the brain.

HPLC is distinguished from traditional ("low pressure") liquid chromatography because operational pressures are significantly higher (around 50–1400 bar), while ordinary liquid chromatography typically relies on the force of gravity to pass the mobile phase through the packed column. Due to the small sample amount separated in analytical HPLC, typical column dimensions are 2.1–4.6 mm diameter, and 30–250 mm length. Also HPLC columns are made with smaller adsorbent particles (1.5–50 μm in average particle size). This gives HPLC superior resolving power (the ability to distinguish between compounds) when separating mixtures in a shorter period of time, which makes it a popular chromatographic technique. The schematic of an HPLC instrument typically includes solvents' reservoirs, one or more pumps, a solvent-degasser, a sampler, a column, and a detector. The solvents are prepared in advance according to the needs of the separation, they pass through the degasser to remove dissolved gasses, mixed to become the mobile phase, then flow through the sampler, which brings the sample mixture into the mobile phase stream, which then carries it into the column. The pumps deliver the desired flow and composition of the mobile phase through the stationary phase inside the column, then directly into a flow-cell inside the detector. The detector generates a signal proportional to the amount of sample component emerging from the column, hence allowing for quantitative analysis of the sample components.

==== Antigonadotropic effects ==== Changes in endogenous testosterone levels may also contribute to differences in myotrophic–androgenic ratio between testosterone and synthetic AAS. AR agonists are antigonadotropic – that is, they dose-dependently suppress gonadal testosterone production and hence reduce systemic testosterone concentrations. By suppressing endogenous testosterone levels and effectively replacing AR signaling in the body with that of the exogenous AAS, the myotrophic–androgenic ratio of a given AAS may be further, dose-dependently increased, and this hence may be an additional factor contributing to the differences in myotrophic–androgenic ratio among different AAS. In addition, some AAS, such as 19-nortestosterone derivatives like nandrolone, are also potent progestogens, and activation of the progesterone receptor (PR) is antigonadotropic similarly to activation of the AR. The combination of sufficient AR and PR activation can suppress circulating testosterone levels into the castrate range in men (i.e., complete suppression of gonadal testosterone production and circulating testosterone levels decreased by about 95%). As such, combined progestogenic activity may serve to further increase the myotrophic–androgenic ratio for a given AAS.

== Personal life == Robinson is a non-denominational Christian and lives in Cave Junction, Oregon. He was married to Laurelee Robinson until her death in 1988. His six children were all home schooled. As a hobby, Robinson buys unwanted pipe organs from churches and reassembles them on his property. Among the instruments in his collection is the organ formerly owned by famed Christian Gospel singer George Beverly Shea.

Based on the size and histological staining characteristics of the fibrils, it is likely that at least in part they are composed of type III collagen (reticulin). An in vitro study with native collagen demonstrated that fibronectin binds to type III collagen rather than other types.

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.

Is CJC-1295 the same as modified GRF(1-29)?

The names are often used interchangeably in casual writing, but they are not strictly identical. Modified GRF(1-29) refers to the unconjugated analogue carrying only the four substitutions. The version sold as CJC-1295 with DAC includes the albumin binding linker and clears much more slowly.

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