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Cjc-1295 Structure And Mechanism — Beginner to Advanced

By Editorial Desk · published 2025-12-09 · last reviewed 2025-12-26 · Wiki

Everything below concerns lyophilisation. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.

Last reviewed on 2025-12-26. Where a claim depends on a specific study, the study is described rather than over-claimed.

CJC-1295 Structure And Mechanism

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.

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.

Handling, Stability and Analysis

Identity and purity are assessed mainly by reversed-phase high-performance liquid chromatography combined with mass spectrometry. The chromatographic separation resolves the target peptide from truncation products and from species carrying oxidised residues, while mass measurement confirms the expected molecular mass. Because the two common variants differ by roughly 280 daltons, a mass determination distinguishes them unambiguously. Purity is often quoted as a percentage of total peak area, although that figure depends on the detection wavelength and the integration method applied.

Reported half-lives differ widely between the two variants and between species. Values for the albumin-binding form are usually expressed in days, while the unconjugated form is measured in minutes to a few hours. Sampling schedules, assay sensitivity, and route of administration all influence the numbers, which limits direct comparison across studies. Whether sustained receptor occupancy produces different downstream effects from pulsatile stimulation remains an open question in the published work. Claims about relative potency should therefore be read alongside the specific study design that produced them.

Lyophilised powder is the usual supplied form. The material is hygroscopic, so vials are typically equilibrated to room temperature before opening in order to prevent condensation on the contents. Long-term storage is generally described at minus twenty degrees Celsius or colder, protected from light and moisture. Repeated freeze-thaw cycles are avoided because they promote aggregation and loss of soluble material. A reconstituted solution is considerably less stable than the dry powder and is normally kept refrigerated for short periods only.

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.

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Background and Molecular Design

CJC-1295 belongs to a family of synthetic peptides modeled on growth hormone-releasing hormone, the hypothalamic signal that prompts the pituitary to release growth hormone. The compound is built from the first twenty-nine amino acids of the natural human sequence, a fragment that retains full receptor binding capacity. Native growth hormone-releasing hormone is degraded quickly in circulation, so the fragment alone has limited practical value. Early work therefore focused on chemical modifications that preserve receptor binding while slowing enzymatic breakdown. The result is a molecule described in the literature as a long-acting analog of the natural hormone.

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.

Receptor Action and Clearance

Clearance profiles diverge sharply between the two versions. The albumin-binding molecule stays in plasma for several days, whereas the unmodified analog is largely gone within about half an hour in reported work. Cleavage by dipeptidyl peptidase IV is a major contributor to the short life of the unmodified sequence. These gaps mean the two versions cannot be substituted for each other in study design or in reading results side by side.

Reports on this compound commonly follow serum growth hormone and insulin-like growth factor 1 across defined time windows. Protocols differ in sampling frequency, assay platform, and participant characteristics, which makes direct comparison between publications difficult. Some work focuses on pulsatile release patterns instead of average concentrations. Whether repeated exposure alters endogenous hormone rhythms over long periods remains an open question, and the formal literature is thinner than the volume of informal commentary implies.

Once in circulation, the peptide binds the growth hormone-releasing hormone receptor displayed on pituitary somatotroph cells. Receptor activation couples to Gs proteins, elevates intracellular cyclic AMP, and drives protein kinase A signaling inside the cell. That cascade increases discharge of growth hormone into the bloodstream. The analog therefore operates through a receptor pathway that already exists for the body's own releasing hormone, rather than through an engineered artificial target.

Reference notes

Funding for research in this field was in part provided by the Muscular Dystrophy Association and the Acid Maltase Deficiency Association in the US and by the Association of Glycogen Storage Disease in the UK, as well as the International Pompe Association. John Crowley became involved in the fund-raising efforts in 1998 after two of his children were diagnosed with Pompe. He joined the company Novazyme in 1999, which was working on enzyme replacement treatment for Pompe. Novazyme was sold to Genzyme in 2001 for over US$100 million. The 2010 film Extraordinary Measures is based on Crowley's search for a cure. As of 2019, many biomedical companies are developing gene therapy in hopes of helping the body create alpha-glucosidase on its own. In 2021, in-utero enzyme replacement therapy infusions were provided to the fetus of an Ottawa, Ontario, mother who had had two previous children with Pompe disease. The medical team was a collaboration between Ottawa Hospital, Children's Hospital of Eastern Ontario, the University of California, San Francisco, and Duke University. The child, born in June 2021, is thriving as of November 2022.

He was also president of the family's principal philanthropy run by family members, the Rockefeller Brothers Fund, from its inception in 1940 to 1956. In 1929, he joined the family's renowned Rockefeller Foundation; elected to the board in 1931 he subsequently became chairman of this major philanthropic organization for twenty years and was responsible for changing the focus of the institution. The principal philanthropic institution he created was the JDR III Fund in 1963, its major program being the Asian Cultural Program, created in 1967 to encourage East-West cultural exchange. The Fund was wound-up upon his death in 1979, but the Cultural Program continued as the Asian Cultural Council, which has provided grant assistance to more than 4,000 Asians and Americans in the area of the arts. Funding for its programs is derived from a combination of endowment income and contributions from individuals, foundations and corporations in the United States and Asia. In the mid-1950s, John III assumed the leadership of the Exploratory Committee for a Musical Arts Center, a committee of civic leaders who were working to create what would become Lincoln Center. He was the key figure in the fund-raising efforts and in forging a consensus among the civic leaders and others who were essential to its success. The Center itself was built over a period from 1959 to 1969. He was its second president, commencing in 1956, and he became its chairman in 1961. He was chairman until 1970 when he was duly elected honorary chairman.

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Sources: en.wikipedia.org

Reference notes

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== Books == Seven and a Half Lessons About the Brain. Houghton Mifflin Harcourt, 2020. ISBN 0358157145. How Emotions are Made: The Secret Life of the Brain. Houghton Mifflin Harcourt, 2017. ISBN 0544133315. Handbook of Emotions, Fourth Edition. Guilford Fubn, 2018 The Psychological Construction of Emotion, Guilford Fubn, 2014

The kinetic energy distribution in the direction of ion flight can be corrected by using a reflectron. The reflectron uses a constant electrostatic field to reflect the ion beam toward the detector. The more energetic ions penetrate deeper into the reflectron, and take a slightly longer path to the detector. Less energetic ions of the same mass-to-charge ratio penetrate a shorter distance into the reflectron and, correspondingly, take a shorter path to the detector. The flat surface of the ion detector (typically a microchannel plate, MCP) is placed at the plane where ions of same m/z but with different energies arrive at the same time counted with respect to the onset of the extraction pulse in the ion source. A point of simultaneous arrival of ions of the same mass-to-charge ratio but with different energies is often referred as time-of-flight focus. An additional advantage to the re-TOF arrangement is that twice the flight path is achieved in a given length of the TOF instrument.

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Sources: en.wikipedia.org

Reference notes

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In the scheme below, please note that the double bond coordinating to tin denotes R2, so any alkenyl, allyl, or aryl group. Furthermore, the X group can dissociate at any time during the mechanism and bind to the Sn+ complex at the end. Density functional theory calculations predict that an open mechanism will prevail if the 2 ligands remain attached to the palladium and the X group leaves, while the cyclic mechanism is more probable if a ligand dissociates prior to the transmetalation. Hence, good leaving groups such as triflates in polar solvents favor the cyclic transition state, while bulky phosphine ligands will favor the open transition state.

In the four tables below, very minor branches of decay (branching probability less than one in a million) are omitted. Spontaneous fission is also omitted, though larger than this for the heaviest even nuclei and detectable down to thorium. All nuclear data is taken from unless otherwise noted. The historical names of isotopes are recorded in. The energy release includes the total kinetic energy of all the emitted particles (electrons, alpha particles, gamma quanta, neutrinos, Auger electrons and X-rays) and the recoiling decay product nucleus; this corresponds to that calculated from atomic masses. The letter 'a' represents a year (from the Latin annus). In the tables (except for the neptunium series), the historical names of the naturally occurring nuclides are also given. Such names were used at the time when the decay chains were first discovered and investigated; the system listed was only finalized in the 1920s but it would be too confusing to give earlier names also. From these historical names one can thus find the modern isotopic designation. The three primordial chains given below—thorium, uranium/radium (from uranium-238), and actinium (from uranium-235)—each ends with its own specific lead isotope (lead-208, lead-206, and lead-207 respectively). All the lead isotopes are stable and are also present in nature as primordial nuclides, so their excess amounts in comparison with lead-204 (which has only a primordial origin) are required for accurate uranium–lead dating of rocks. Correlating more than one results in lead-lead dating, capable of even greater accuracy.

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.

Why is mass spectrometry used alongside chromatography?

Chromatography reports how much material elutes as a single peak but does not confirm what that material is. Mass spectrometry supplies the molecular mass, which is characteristic of a given sequence and its modifications. Together the two methods support both a purity figure and an identity claim.

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