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Structure And Receptor Pharmacology — Practical Notes

By Editorial Desk · published 2025-11-20 · last reviewed 2026-01-08 · Info

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

This page was last updated on 2026-01-08 and is reviewed periodically as new material appears.

Structure And Receptor Pharmacology

CJC-1295 belongs to a class of synthetic peptides modeled on growth hormone releasing hormone, a forty-four amino acid signal produced by the hypothalamus. The compound is built from the first twenty-nine residues of the natural sequence, with four substitutions introduced at positions 2, 8, 15 and 27. These changes were designed to slow enzymatic breakdown while preserving receptor activation. The result is a peptide that is shorter than native GHRH and considerably more resistant to ordinary clearance pathways in circulation.

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 Background and Mechanism

CJC-1295 is a synthetic peptide designed to mimic growth hormone-releasing hormone (GHRH), the endogenous signal that prompts the pituitary gland to release growth hormone. The compound is a modified fragment of the natural hormone, spanning the first twenty-nine amino acids of GHRH with several substitutions that slow enzymatic breakdown. Two variants circulate in research settings: one carrying a drug affinity complex (DAC) and one without it. The DAC-free form is frequently labelled Mod GRF(1-29) in catalogs and discussion forums.

The peptide binds GHRH receptors on somatotroph cells within the anterior pituitary, triggering a signalling cascade that increases growth hormone secretion. Its improved resistance to dipeptidyl peptidase IV degradation distinguishes it from the parent hormone. In the DAC-bearing version, a maleimide group reacts with a cysteine residue on serum albumin, forming a covalent bond that keeps the peptide in circulation far longer. That albumin attachment is the central design feature separating the two research variants.

Pharmacokinetic behaviour differs sharply between the two forms. The DAC-bearing peptide shows an extended circulation time measured in days, whereas the version without the complex is cleared within roughly half an hour. This gap shapes how researchers design dosing schedules in animal models. Whether the prolonged presence of the DAC form produces effects meaningfully different from the short-acting variant remains an open question, since comparative human data are scarce.

Cjc-1295 at a glance

PropertyValueNotes
Peptide classSynthetic GHRH analogueBuilt on a 29 residue sequence
Primary targetGHRH receptor (GHRHR)Class B G protein coupled receptor
Unconjugated half lifeMinutesLimited by protease degradation
Key modificationFour residue substitutionsPositions 2, 8, 15 and 27
Common synonymModified GRF(1-29)Usually denotes the form without DAC

Handling, Stability and Analysis

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.

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.

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Background and Naming Conventions

CJC-1295 is a synthetic peptide analog of growth hormone-releasing hormone, constructed on the 29-amino-acid fragment designated GRF(1-29). The name began as an internal development code during the 1990s and later spread through research supply catalogs and discussion forums. The molecule does not occur in nature; its sequence is engineered rather than isolated from tissue. Two related compounds are sold under this single label, and they differ by one appended chemical group that strongly influences how long the peptide remains in circulation.

The dividing feature between the two forms is a maleimide-based drug affinity complex, abbreviated DAC. In the DAC-bearing version, a linker attaches the peptide to serum albumin after administration, and that association slows removal from plasma. The version lacking DAC appears in catalogs as MOD GRF(1-29) or tetrasubstituted GRF(1-29). Because informal writing treats both as one item, comparisons drawn from such sources routinely blend measurements taken from two molecules with substantially different behavior.

Further detail

John J. Abel Award Julius Axelrod Award Pharmacia-ASPET Award in Experimental Therapeutics Robert R. Ruffolo Career Achievement Award Travel Award for Pharmacology Educators Bernard B. Brodie Award in Drug Metabolism P.B. Dews Lifetime Achievement Award for Research in Behavioral Pharmacology Drug Metabolism Early Career Achievement Award Goodman and Gilman Award in Receptor Pharmacology Benedict R. Lucchesi Distinguished Lectureship in Cardiac Pharmacology Torald Sollmann Award in Pharmacology Paul M. Vanhoutte Distinguished Lectureship in Cardiovascular Pharmacology Travel awards to participate in its meetings are also given to students and postdocs. Chemotherapy Clinical pharmacology Drug metabolism Neuropharmacology Pharmacology Toxicology Official website Molecular Interventions magazine

First observations of short-lived pear-shaped atomic nuclei Research conducting using the Miniball experimental setup found evidence of pear-shaped heavy nuclei, in particular radon-220 and radium-224. These results were named in the Institute of Physics (IoP) "top 10 breakthroughs in physics" in 2013, and was featured as the cover of Nature 2013. In 2020, due to the HIE-ISOLDE upgrade, radium-222 was also found to have a "stable pear shape". Laser spectroscopy has been performed on a short-lived radioactive molecule, containing radium, which further studies into could reveal physics beyond the Standard Model due to time-reversal symmetry breaking. Measurement of 229mTh transition energy In 2023, ISOLDE made the first 1%-level measurement of the ultralow-energy thorium-229m nuclear isomer, detecting photons at an energy of 8.338±0.024 eV. This was a key step in the construction of a future nuclear clock. Below is a list of improvements needed for the ISOLDE facility, considering both medium and long-term goals. Some of these improvements have been proposed by the EPIC project.

The tine test, which uses a "button" with four to six short needles coated with tuberculin instead of an injection. It is easier to administer. It has comparable results if "doubtful" indications are treated as positive. The US CDC and the American Thoracic Society believe that it is less reliable because the amount of tuberculin that enters the skin cannot be accurately determined, despite the aforementioned results. The Heaf test, a test similar to the tine test formerly used in the United Kingdom. A spring-loaded instrument with six needles is used. It stopped being used in 2005 as the manufacturer deemed the production of this instrument financially unsustainable.

Sources: en.wikipedia.org

Supporting material

76. Hydromorphone. Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006–. 2026 Sep 15. Limited data indicate that hydromorphone is excreted into breastmilk in small amounts, but large maternal dosages have caused neonatal central nervous system depression. In general, Maternal use of oral opioids during breastfeeding can cause infant drowsiness, which may progress to rare but severe central nervous system depression. Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. If hydromorphone is required by the mother of a newborn, it is not a reason to discontinue breastfeeding; however, once the mother’s milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of hydromorphone to 2 to 3 days at a low dosage with close infant monitoring.[1] If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped.

== Animal harvesting == When not synthesized, collagen can be harvested from animal skin. This has led to deforestation, as has occurred in Paraguay, where large collagen producers buy large numbers of cattle hides from regions that have been clear-cut for cattle grazing.

In a typical nuclear reactor fueled with uranium-235, the presence of 135Xe as a fission product presents designers and operators with problems due to its large neutron cross section for absorption. Because absorbing neutrons can impair a nuclear reactor's ability to increase power, reactors are designed to mitigate this effect and operators are trained to anticipate and react to these transients. This practice dates to the first fission piles, constructed by the Manhattan Project during the Second World War. Enrico Fermi suspected that 135Xe would act as a powerful neutron poison and followed the advice of Emilio Segrè by contacting his student Chien-Shiung Wu. Wu's unpublished paper on 135Xe verified Fermi's guess that it absorbed neutrons and was the cause of the disruptions to the B Reactor then in use at Hanford, Washington to breed plutonium for the American implosion bomb. During periods of steady state operation at a constant neutron flux level, the 135Xe concentration builds up to its equilibrium value for that reactor power in about 40 to 50 hours. When the reactor power is increased, 135Xe concentration initially decreases because the burn up is increased at the new higher power level. Because 95% of the 135Xe production is from decay of 135I, which has a 6.58 hour half-life, the production of 135Xe remains constant; at this point, the 135Xe concentration reaches a minimum. The concentration then increases to the new equilibrium level (more accurately steady state level) for the new power level in roughly 40 to 50 hours.

Sources: pubmed.ncbi.nlm.nih.gov

Frequently asked questions

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.

What does the acronym DAC refer to?

DAC stands for drug affinity complex, a term describing the maleimidopropionic acid linker. This group forms a covalent bond with the cysteine residue on serum albumin after administration. The resulting adduct is what extends the circulating half life from minutes to days.

Does this peptide occur naturally in the body?

No. It is entirely synthetic and does not correspond to any known endogenous peptide. The design starts from human growth hormone releasing hormone and introduces deliberate substitutions. Any biological effect comes from mimicking the natural hormone at its receptor.

What distinguishes CJC-1295 from natural GHRH?

The synthetic peptide keeps the receptor-binding region of GHRH but carries substitutions that resist enzymatic cleavage. In the DAC version, an added group also anchors the molecule to albumin, extending its presence in the bloodstream.

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