CJC-1295 with DAC is a growth hormone-releasing hormone (GHRH) analog engineered to bind serum albumin after it enters circulation. It combines a stabilized 29-residue GHRH backbone with a reactive maleimide group, the Drug Affinity Complex (DAC), that forms a covalent bond with albumin. The conjugate persists far longer than any free GHRH peptide.
That long persistence is what made the molecule interesting to endocrinologists: it allowed researchers to ask what happens to the growth hormone axis under a continuous GHRH signal rather than brief pulses. The sections below cover how the DAC strategy was developed, the chemistry of albumin binding, the key rodent and clinical pharmacology studies, and the gaps that remain.
At a glance
- Class: Synthetic GHRH(1-29) analog with albumin-binding Drug Affinity Complex; GHRH receptor agonist
- Origin: ConjuChem (Montreal); identified as a long-lasting analog by Jetté and colleagues in 2005
- Structure: 30 residues: Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Ser-Arg-Lys(Nε-maleimidopropionyl)-NH2; C165H269N47O46; 3647.2 g/mol; CAS 446262-90-4
- Main research areas: albumin bioconjugate pharmacology, GH pulsatility under continuous stimulation, GHRH-deficient mouse models, anti-doping detection
- Regulatory status: Not FDA approved; WADA S2
Structure and origin
Native GHRH(1-29) is cleared from plasma within minutes. Two processes dominate: dipeptidyl peptidase-4 removes the first two residues, and the kidneys filter the small peptide quickly. Researchers at ConjuChem attacked both at once. They started with a GRF(1-29) backbone carrying four substitutions (D-Ala2, Gln8, Ala15, Leu27) that resist enzymatic cleavage, deamidation and oxidation. They then added a lysine at position 30 and attached a maleimidopropionic acid group to its side-chain amine.
Maleimides react selectively with free thiol groups. Human serum albumin carries one unpaired cysteine, Cys34, which is exposed and reactive. Once the peptide meets albumin, the maleimide forms a stable thioether bond with that cysteine. The resulting complex has the size of albumin, roughly 66 kDa, which keeps it out of the glomerular filtrate and shields much of the peptide from proteases.
In the 2005 study, Jetté and colleagues prepared a series of GRF(1-29) analogs with the reactive group at different positions, preformed or allowed to form albumin conjugates, and tested them in rats. They measured whether the conjugates still activated the GRF receptor in the anterior pituitary and how long GH responses lasted. The analog now called CJC-1295 retained receptor activity after albumin binding and gave the most durable response (Jetté et al., 2005).
Mechanism: what the research shows
The target is the GHRH receptor, a class B G protein-coupled receptor found mainly on pituitary somatotrophs and cloned in 1992 (Mayo, 1992). It signals through Gs and cAMP to stimulate GH synthesis and release. The albumin conjugate does not change the receptor or the pathway; it changes how long the agonist is available.
A central question was whether constant receptor exposure would desensitize the system or erase the normal pulsatile pattern of GH secretion. In a clinical study using frequent blood sampling, Ionescu and Frohman found that GH pulses persisted during continuous stimulation with CJC-1295, with increased trough levels between pulses (Ionescu and Frohman, 2006). That finding is important for interpreting experiments with long-acting GHRH agonists, because it suggests that somatostatin and other upstream controls keep shaping the output even when the GHRH signal is sustained.
Key areas of study
Albumin bioconjugate design
CJC-1295 is a frequently cited example of the in vivo albumin-binding approach for extending peptide half-life. The 2005 rat study is the foundational paper and includes the structure-activity comparisons that led to the selected analog (Jetté et al., 2005).
GHRH-deficient mouse models
Alba and colleagues tested CJC-1295 in GHRH knockout mice, which lack endogenous GHRH and have reduced GH and growth. They compared several treatment schedules and measured body weight, body length and pituitary GH axis markers. In this model, daily exposure was associated with growth parameters approaching those of wild-type animals, while less frequent schedules gave partial effects (Alba et al., 2006). The study is one of the clearest demonstrations that a long-acting GHRH signal can sustain GH axis activity in a GHRH-deficient animal.
Clinical pharmacology
CJC-1295 was evaluated in healthy adults in a pharmacokinetic and pharmacodynamic study that documented its long half-life and prolonged GH and IGF-1 responses (Teichman et al., 2006). The companion pulsatility study is described above (Ionescu and Frohman, 2006). Clinical development did not lead to an approved product.
Analytical detection
CJC-1295 has been identified in an unknown pharmaceutical preparation submitted for analysis, with mass spectrometry used to confirm its structure (Henninge et al., 2010). Detection methods for GHRH analogs are an active anti-doping research topic.
What the evidence does not show
- The peer-reviewed literature specific to CJC-1295 is small: a handful of core papers from the developer and collaborators, plus analytical reports.
- Rodent data come mainly from rats and GHRH knockout mice; knockout animals have a defect the molecule is designed to fill, so results there may not extend to intact animals.
- Clinical studies were short-term pharmacology trials. They do not establish long-term safety, and the program did not produce an approved drug.
- Material sold as “CJC-1295” varies in the market; without the DAC group it is a different molecule with very different kinetics, which makes batch identity testing essential.
Regulatory status
CJC-1295 has been evaluated in clinical studies but is not approved by the FDA or any other major regulator. The World Anti-Doping Agency lists it under S2 (peptide hormones, growth factors, related substances and mimetics). Rogue Compounds sells it as a research reagent only.
Handling and storage in the lab
Keep the lyophilized peptide sealed and refrigerated at 2–8°C (36–46°F), protected from light.
Sourcing and documentation
Rogue Compounds has CJC-1295 (DAC) made in small batches. Every vial carries a batch number and a QR code that opens the independent U.S. testing lab’s own report for that batch, and the same batch COA is on the product page and in the COA Library.
View CJC-1295 (DAC) on Rogue Compounds
References
- Jetté L, et al. Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology. 2005;146(7):3052-3058. PMID 15817669
- Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PMID 1333056
- Alba M, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-E1294. PMID 16822960
- Teichman SL, et al. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. PMID 17018654
- Henninge J, et al. Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation. Drug Test Anal. 2010;2(11-12):647-650. PMID 21204297
Research use only. Rogue Compounds products are sold strictly for laboratory research. They are not for human or veterinary use, and nothing in this article is medical advice. The studies cited here describe published research, not this product or any use of it.