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Cjc-1295 Structure And Mechanism — Background and Details

By Editorial Desk · published 2026-05-20 · last reviewed 2026-06-09 · Topic

The short version of Cyclic AMP fits in a sentence. The long version — which is the one that helps — is below.

Reviewed 2026-06-09. Anything still debated is marked as such rather than presented as settled.

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.

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.

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

Reference notes

== Synthesis == Shortly after Merck initiated research into reducing the severity and likelihood of chemotherapy-induced nausea and vomiting, researchers discovered that aprepitant is effective in prevention. Researchers worked on coming up with a process to create aprepitant, and within a short period they came up with effective synthesis of the substance. This original synthesis was deemed to be workable and proved to be a crucial step in achieving commercialization; however, Merck decided that the process was not environmentally sustainable. This was due to the original synthesis requiring six steps, many of which needed dangerous chemicals such as sodium cyanide, dimethyltitanocene, and gaseous ammonia. In addition to this, for the process to be effective cryogenic temperatures were needed for some of the steps and other steps produced hazardous byproducts such as methane. The environmental concerns of the synthesis of aprepitant became so great that Merck research team decided to withdraw the drug from clinical trials and attempt to create a different synthesis of aprepitant. The gamble of taking the drug out of clinical trials proved to be successful when shortly afterwards the team of Merck researchers came up with an alternative and more environmentally friendly synthesis of aprepitant. The new process works by four compounds of similar size and complexity being fused together. This therefore is a much simpler process and requires only three steps, half the number of the original synthesis.

=== Absorption === Bicalutamide is extensively and well-absorbed following oral administration, and its absorption is not affected by food. The absolute bioavailability of bicalutamide in humans is unknown due to its very low water solubility and hence lack of an assessable intravenous formulation. However, the absolute bioavailability of bicalutamide has been found to be high in animals at low doses (109% in mice at 10 mg/kg; 72% in rats at 1 mg/kg; 100% in dogs at 0.1 mg/kg), but diminishes with increasing doses such that the bioavailability of bicalutamide is low at high doses (10% in rats at 250 mg/kg; 31% in dogs at 100 mg/kg). In accordance, absorption of (R)-bicalutamide in humans is slow and extensive but saturable, with steady-state levels increasing linearly at a dosage of up to 150 mg/day and non-linearly at higher dosages. At higher dosages of 100 to 200 mg/day, absorption of bicalutamide is approximately linear, with a small but increasing departure from linearity above 150 mg/day. In terms of geometric mean steady-state concentrations of (R)-bicalutamide, the departures from linearity were 4%, 13%, 17%, and 32% with dosages of 100, 150, 200, and 300 mg/day, respectively. There is a plateau in steady-state levels of (R)-bicalutamide with bicalutamide dosages above 300 mg/day, and, accordingly, dosages of bicalutamide of 300 to 600 mg/day result in similar circulating concentrations of (R)-bicalutamide and similar degrees clinically of efficacy, tolerability, and toxicity.

The first point to note is that, when pKa is positive, the standard free energy change for the dissociation reaction is also positive. Second, some reactions are exothermic and some are endothermic, but, when ΔH⊖ is negative TΔS⊖ is the dominant factor, which determines that ΔG⊖ is positive. Last, the entropy contribution is always unfavourable (ΔS⊖ < 0) in these reactions. Ions in aqueous solution tend to orient the surrounding water molecules, which orders the solution and decreases the entropy. The contribution of an ion to the entropy is the partial molar entropy which is often negative, especially for small or highly charged ions. The ionization of a neutral acid involves formation of two ions so that the entropy decreases (ΔS⊖ < 0). On the second ionization of the same acid, there are now three ions and the anion has a charge, so the entropy again decreases. Note that the standard free energy change for the reaction is for the changes from the reactants in their standard states to the products in their standard states. The free energy change at equilibrium is zero since the chemical potentials of reactants and products are equal at equilibrium.

The space inside the root canals is filled with a highly vascularized, loose connective tissue, called dental pulp. The dental pulp is the tissue of which the dentin portion of the tooth is composed. The dental pulp helps complete formation of the secondary teeth (adult teeth) one to two years after eruption into the mouth. The dental pulp also nourishes and hydrates the tooth structure, making the tooth more resilient, less brittle and less prone to fracture from chewing hard foods. Additionally, the dental pulp provides a hot and cold sensory function.

Sources: en.wikipedia.org

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Notes from published material

=== Colon Treaty of Peace and Friendship === On August 26, 1876, the Grand Lodge of Colon in Santiago de Cuba declared itself entirely independent as a sovereign Masonic Body with its own full and unlimited powers over its own subordinate lodges. Under their auspices, the Grand Lodge of Colon possessed 36 lodges and 8,000 members. On November 24, 1876, the Grand Lodge of Colon and the Supreme Council of Colon signed the Tratado de Paz y Amistad (English: Treaty of Peace and Friendship). This treaty was based in the agreements of the Lausanne Congress. It degraded the superior prestige of the higher degrees, eliminated authoritarian positions at the Supreme Council, ejected the Spanish aristocracy from holding undue power, and erased the mystical positions. The Supreme Council of Colon recognized the Grand Lodge of Colon as "regular and correct," and also recognized their authority over the three degrees of the Blue Lodge. The Grand Lodge recognized the Supreme Council as the authority over the 4th to 33rd degrees.

== Scope of accreditation == NABL's scope for accreditation extends to:- Testing Laboratories: Biological, Chemical, Diagnostic Radiology QA testing, Electrical, Electronics, Fluid-Flow, Forensic, Mechanical, Non-Destructive testing, Photometry, Radiological and Software & IT system testing. Calibration Laboratories: Electro-Technical, Mechanical, Fluid Flow, Thermal & Optical, Radiological, Thermal. Medical Laboratories: Clinical Biochemistry, Clinical Pathology, Haematology & Immunohaematology, Microbiology and Infectious Disease Serology, Molecular Diagnostics, Histocompatibility & Immunogenetics, Medical Imaging, Histopathology, Cytopathology, Flow cytometry, Cytogenetics.

=== Phase 2 === Desmethylcariprazine prodrug (ABBV-932; RGH-932) – dopamine D2 and D3 receptor partial agonist and other actions [7] ENX-102 (ENX102) — α2, α3, and α5 subunit-containing GABAA receptor positive allosteric modulator and nonbenzodiazepine FKW-00GA (FKW00GA; TGW-00AA; TGW00AA) – serotonin 5-HT1A receptor partial agonist and serotonin 5-HT2A receptor antagonist [8] Lumateperone deuterated (ITI-1284) – atypical antipsychotic (non-selective monoamine receptor modulator [9] ONO-1110 – endocannabinoid synthesis regulator and indirect cannabinoid receptor modulator [10] [11] [12] TGFK-08AA (TGFK08AA) – serotonin 5-HT1A receptor modulator [13] Vortioxetine (Brintellix; Lu-AA21004; Trintellix; Vortidif) – serotonin reuptake inhibitor, serotonin 5-HT1A and 5-HT1B receptor agonist, and serotonin 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist [14]

=== Motivational disorders === Selegiline has been found to produce pro-motivational effects and to reverse motivational deficits in rodents. In case reports and small clinical studies, selegiline has been reported to improve disorders of diminished motivation like apathy and abulia due to conditions such as traumatic brain injury. In accordance with the preceding findings, selegiline, along with other dopaminergic and activating agents, may be useful in the treatment of disorders of diminished motivation, including apathy, abulia, and akinetic mutism.

=== Basicity expressed as dissociation constant of conjugate acid === Because the relationship pKb = pKw − pKa holds only in aqueous solutions (though analogous relationships apply for other amphoteric solvents), subdisciplines of chemistry like organic chemistry that usually deal with nonaqueous solutions generally do not use pKb as a measure of basicity. Instead, the pKa of the conjugate acid, denoted by pKaH, is quoted when basicity needs to be quantified. For base B and its conjugate acid BH+ in equilibrium, this is defined as

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.

Which receptor does the compound target?

It acts on the growth hormone-releasing hormone receptor found on pituitary somatotroph cells. Activation of that receptor triggers growth hormone release through a cyclic AMP dependent pathway.

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