CJC 1295 with DAC is a synthetic analogue of growth hormone-releasing hormone (GHRH) in which a modified 29-residue peptide carries a reactive linker that binds covalently to serum albumin. Laboratory studies use it to examine GHRH receptor signalling, the regulation of growth hormone secretion and the pharmacology of half-life extension by albumin conjugation in cell culture and animal models. The “DAC” in the name stands for drug affinity complex, and it changes the behaviour of the molecule so much that results cannot be shared with the unconjugated form. This article summarises the structure, mechanism, published research and the analytical and storage standards needed for reproducible work. It offers no guidance on human use.
What is CJC 1295 with DAC?
CJC-1295 with DAC is classified as a long-acting synthetic GHRH analogue. Its peptide backbone is modified GRF(1-29), derived from the shortest fragment of human GHRH that retains full receptor activity. Four substitutions relative to the native fragment are usually described: D-alanine at position 2, glutamine at position 8, alanine at position 15 and leucine at position 27. These changes make the peptide resistant to cleavage by dipeptidyl peptidase IV (DPP-IV) and stabilise its helical structure. The C-terminus is amidated.
The distinguishing feature is the DAC itself. A lysine residue at the C-terminal end of the peptide carries a maleimidopropionamide linker. The maleimide group reacts with the free thiol on cysteine 34 of serum albumin, forming a covalent bond. Once the peptide is bound, it travels with albumin, which has a half-life measured in weeks, and is cleared far more slowly than the free peptide, whose half-life is a matter of minutes. The molecular weight of the conjugatable peptide is approximately 3647 Da, although the exact figure depends on the stated structure and salt form and should be taken from the certificate of analysis.
The compound was developed by the Canadian biotechnology company ConjuChem as part of a platform for albumin-conjugated peptides. The first published description of conjugated GHRH analogues came from Jetté and colleagues in 2005 in the journal Endocrinology, which identified CJC-1295 as a long-lasting analogue in rats. The approach was later reported in a clinical pharmacology setting in healthy adult volunteers.
The product-naming point is important for buyers. The supply market uses “CJC-1295” for two different molecules. CJC 1295 with DAC is the albumin-binding form described here. The form often sold as “CJC-1295 No DAC” is, chemically, modified GRF(1-29) without the linker, with a molecular weight of about 3368 Da and a very short half-life. A certificate of analysis should state which one is supplied, and the mass found shows it clearly, because the difference is close to 280 Da.
Regulatory context matters for any UK buyer. CJC-1295 is not authorised as a medicine in the United Kingdom, and it appears on the World Anti-Doping Agency prohibited list. The Medicines and Healthcare products Regulatory Agency (MHRA) has issued warnings about unlicensed products marketed for human use. The material is relevant here only as a laboratory research reagent.
Mechanism of action
CJC 1295 with DAC is an agonist at the GHRH receptor (GHRH-R), a class B G protein-coupled receptor expressed mainly on somatotroph cells of the anterior pituitary. The receptor is engaged through two sites. The C-terminal part of the peptide binds the large extracellular domain, and the N-terminal region inserts into the transmembrane core to trigger activation. Receptor activation stimulates the G protein Gs, which activates adenylyl cyclase and raises intracellular cyclic AMP (cAMP). Protein kinase A is then activated, and phosphorylation of transcription factors including CREB promotes expression of the growth hormone gene and of the pituitary transcription factor Pit-1. The same pathway increases the release of stored growth hormone from secretory granules.
In an intact animal, released growth hormone acts on peripheral tissues, notably the liver, to stimulate production of insulin-like growth factor 1 (IGF-1), and the axis is regulated by negative feedback from IGF-1 and by somatostatin. A central question about long-acting analogues has been whether continuous receptor occupation abolishes the natural pulsatile pattern of secretion or preserves it.
The albumin-binding property adds a layer of pharmacology that the unconjugated peptide lacks. Once the peptide is attached, it behaves as a slowly dissociating reservoir, and its apparent activity depends on albumin concentration in the system. Whether the albumin-bound peptide can engage the receptor directly, or acts through a small free fraction in equilibrium, is a point studied in the original pharmacology. For laboratory design, the consequence is that serum-free and serum-containing media will give different effective concentrations, so the medium should always be reported.
In cell-based work, the mechanism is usually tested in receptor-expressing cell lines or primary pituitary cultures. Readouts include cAMP accumulation, cAMP-response element reporter assays and growth hormone released into the medium, from which concentration-response curves and EC50 values are built. In these systems, “dosage” means molar concentration in the medium, which depends on net peptide content, the extent of conjugation, adsorption to plasticware and protease activity in any serum used.
What the research shows
The published literature on CJC-1295 is limited compared with many research peptides, and much of it is concentrated in a few papers from the mid-2000s. Four areas are summarised below in general terms. Readers should consult the primary papers for methods, concentrations and statistics, because commercial summaries often overstate findings.
The first area is the original preclinical work on albumin-conjugated GHRH analogues. Jetté and colleagues, working with ConjuChem, described bioconjugates of GRF(1-29) that bound serum albumin and activated the GHRH receptor in rats, and they reported that conjugation prolonged the duration of growth hormone-stimulating activity relative to the unconjugated peptide. Exposures in the rat experiments were expressed per kilogram of body weight, and the values should be taken from the paper. The study can be located through a PubMed search for the albumin bioconjugate GRF study in rats.
The second area is a clinical pharmacology study by Teichman and colleagues, published in the Journal of Clinical Endocrinology and Metabolism in 2006. It examined the pharmacokinetics and pharmacodynamics of CJC-1295 in healthy adult volunteers under a clinical research protocol, and reported a half-life of days and sustained increases in plasma growth hormone and IGF-1 concentrations. This was a clinical investigation conducted under ethical approval, and it is cited here only as part of the scientific record. It says nothing about research-grade material, and nothing in this article describes a use outside such a setting.
The third area concerns the pattern of secretion. Ionescu and Frohman, also in the Journal of Clinical Endocrinology and Metabolism in 2006, asked whether pulsatile growth hormone release persisted during continuous stimulation by CJC-1295, and reported that pulsatility continued with raised baseline levels. This is relevant to experimental design in any system where the temporal pattern of receptor stimulation is a variable. The topic can be explored through a PubMed search on pulsatile GH secretion during continuous CJC-1295 stimulation.
The fourth area is the broader literature on albumin conjugation as a half-life strategy. Studies of other peptides conjugated to albumin, or modified to bind it non-covalently through fatty-acid chains, describe how binding alters clearance, distribution and receptor engagement. CJC-1295 appears in methodological discussions as an example of covalent conjugation, as opposed to the reversible binding used in other designs.
A recurring limitation runs through this body of work. Few studies exist, most are from a small number of groups, and the compound sold in the research market is not always documented as the conjugated form. Reproducibility therefore depends on knowing exactly what was in the vial.
Research applications
In the laboratory, CJC 1295 with DAC is used in several contexts. The most common is as a reference agonist in GHRH receptor pharmacology, where it is used to characterise signalling, benchmark novel agonists and antagonists, and validate cAMP and reporter assays. Because of albumin binding, it is also useful for studying how conjugation changes apparent potency in media of differing albumin content.
A second context is the study of pharmacokinetic engineering. Covalent albumin conjugation is a well-known strategy for extending half-life, and CJC-1295 is an example in discussions of how a reactive linker alters clearance and distribution. Researchers developing other conjugated peptides sometimes use it as a comparator.
A third context is neuroendocrine physiology in animal models, where long-acting analogues are used to probe the dynamics of the growth hormone axis, the role of somatostatin tone and the balance between pulsatile and tonic stimulation. These experiments require institutional ethical review and, in the United Kingdom, authorisation under the Animals (Scientific Procedures) Act 1986.
A fourth context is analytical and anti-doping science. GHRH analogues appear on the World Anti-Doping Agency prohibited list, and reference samples of defined identity and purity are used to develop and validate liquid chromatography and mass spectrometry methods for their detection, including methods that must distinguish the conjugated peptide from its unconjugated counterpart. For this purpose, accurate mass and confirmed linker chemistry are essential.
Across these settings, the sensible meaning of exposure is a defined concentration or per-kilogram quantity, justified by prior literature and verified by analytical characterisation of the material actually used.
Purity, storage and handling
A 29-residue peptide with a reactive linker is more demanding to make and characterise than a short linear peptide. Solid-phase synthesis of that length accumulates truncated and deletion sequences, racemised products and protecting-group adducts, and the maleimide linker adds a chemically reactive group that can hydrolyse, dimerise or react with other nucleophiles during storage. Reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 214 or 220 nm is the standard purity method, and a main peak of at least 98 per cent is commonly expected for receptor pharmacology work. A shallow gradient is needed to resolve closely related impurities, and a stated purity is meaningful only if the method and chromatogram are available.
HPLC must be paired with mass spectrometry. The expected mass is about 3647 Da for the linker-bearing peptide. A species near 3368 Da would indicate the peptide without the linker, which is a different compound, and a mass about 16 Da higher than expected suggests oxidation. A hydrolysed maleimide, which can no longer bind albumin, has a mass about 18 Da higher than the intact linker, and this is one reason the mass spectrum matters for a conjugatable peptide. A clean peak at the wrong mass is a clean peak of the wrong compound.
A batch-specific certificate of analysis matters because purity, peptide content and the integrity of the reactive linker can all vary between synthesis runs and with storage. It should carry a lot number matching the vial, the HPLC trace or purity value, the observed and theoretical masses, the test date and ideally the salt form and net peptide content. Lyophilised powders contain counterions and residual water, so the weighed mass is not the mass of peptide, and ignoring this introduces systematic errors into any concentration-response comparison.
Because the linker can hydrolyse once the peptide is in solution, and because degradation accelerates for a peptide of this length, batch-level verification matters more here than with more robust compounds. UK laboratories sourcing CJC 1295 With Dac should expect a batch-specific certificate of analysis that states the mass found and confirms the linker, with lyophilised storage at -20°C, and the same documentation standard applies when weighing any best peptides supplier uk claim, since a supplier’s analytical record rather than its search ranking shows whether the vial matches its stated specification.
Lyophilised CJC-1295 with DAC is generally stored at -20°C in a sealed container with desiccant, and many laboratories use -80°C for long-term archives. Vials should reach room temperature before opening so that condensation does not form on the cold powder. After reconstitution, stability falls. Standard practice is to dissolve the peptide in sterile water or a suitable buffer, divide the solution into single-use aliquots and freeze them to avoid repeated freeze-thaw cycles. Refrigerated storage at 2 to 8°C is sometimes used for solutions consumed within days, but the acceptable period should be validated for the assay concerned, preferably by re-running HPLC and mass spectrometry on stored solution. Buffers containing free thiols, such as dithiothreitol or mercaptoethanol, will react with the maleimide and should be avoided, and neutral to alkaline pH accelerates both maleimide hydrolysis and deamidation.
Light sensitivity is a secondary but genuine concern. The tyrosine, phenylalanine and methionine-free sequence is less vulnerable than many, but aromatic residues can still undergo photo-oxidation, so amber vials or dark storage are advisable. Peptides also adsorb to glass and some plastics at low concentrations, so low-bind tubes are preferred for dilute working solutions.
Labelling is a final indicator of quality. Clear naming that states whether the product carries the DAC linker, with sequence, molecular weight, lot number, salt form and an unambiguous research-only statement, suggests a supplier that understands its market. Wording that implies use in humans is a warning sign and raises regulatory concerns in the United Kingdom.
Frequently asked questions
What is CJC 1295 with DAC used for in laboratory research?
It is used as a long-acting reference agonist at the GHRH receptor in cell-based pharmacology, in studies of albumin-conjugation and half-life extension, in approved animal work on the growth hormone axis and as a reference material in anti-doping methods. It is a research reagent and not an authorised medicine in the United Kingdom.
What does DAC mean in CJC-1295?
DAC stands for drug affinity complex, a reactive maleimide linker that binds covalently to serum albumin. This extends the half-life from minutes to days in vivo. The form without it, often sold as No DAC, is modified GRF(1-29) and behaves very differently, so results cannot be shared between them.
How should CJC 1295 with DAC be stored for research?
Keep lyophilised peptide at -20°C, or -80°C for long-term archiving, in a sealed, dry, light-protected container. Allow vials to reach room temperature before opening. After reconstitution, aliquot and freeze the solution, and avoid buffers containing free thiols that react with the linker.
How can I verify the quality of a CJC-1295 with DAC batch?
Request a batch-specific certificate showing HPLC purity and a mass spectrometry result near 3647 Da confirming the linker, with a lot number matching the vial. A mass near 3368 Da suggests the unconjugated peptide. For critical work, independent testing by an accredited laboratory confirms identity and purity.
CJC 1295 with DAC is supplied for in-vitro laboratory research only and is not intended for human or veterinary use.
