CJC-1295 DAC, also designated as DAC:GRF (drug affinity complex:growth hormone-releasing factor), represents a synthetic peptide analogue of growth hormone-releasing hormone (GHRH) functioning as a growth hormone secretagogue. Developed by ConjuChem Biotechnologies, this peptide constitutes a modified form of GHRH (1-29) with enhanced pharmacokinetic properties, particularly regarding half-life extension.
The peptide operates as a growth hormone secretagogue by stimulating the anterior pituitary gland to release growth hormone. The fundamental mechanism involves binding to GHRH receptors, triggering cascaded cellular responses that result in increased growth hormone production and subsequent insulin-like growth factor 1 (IGF-1) elevation.
Chemical Structure and Mechanism
Molecular Composition
CJC-1295 consists of a 30-amino acid sequence derived from the first 29 amino acids of GHRH with strategic substitutions and an additional lysine residue at position 30. The IUPAC modification nomenclature identifies the peptide as Nɛ30-maleimidopropionyl-[D-Ala2, Gln8, Ala15, Leu27]-Sermorelin-Lys30.
The complete amino acid sequence follows this structure: H-Tyr-D-Ala2-Asp-Ala-Ile-Phe-Thr-Gln8-Ser-Tyr-Arg-Lys-Val-Leu-Ala15-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu27-Ser-Arg-(Nɛ-maleimidopropionyl-)Lys30-NH2
Drug Affinity Complex (DAC) Technology
The DAC component represents the critical differentiating feature of CJC-1295. This technology involves bioconjugation of a reactive maleimidoproprionic acid group to the lysine residue at position 30. The bioconjugation process creates a covalent bond between the peptide and albumin proteins circulating in the bloodstream.
The albumin-binding mechanism prevents enzymatic degradation and significantly extends the peptide’s biological half-life. This Drug Affinity Complex binds to albumin, creating a reservoir effect that allows for sustained hormone release over extended periods.
Pharmacokinetics and Physiological Effects
Half-Life and Bioavailability
Standard GHRH peptides typically demonstrate half-lives of approximately 30 minutes due to rapid enzymatic degradation. The DAC modification extends CJC-1295’s half-life to 6-8 days in humans, representing a substantial pharmacokinetic improvement.
Clinical research demonstrates that CJC-1295 may markedly increase plasma growth hormone and insulin-like growth factor 1 levels in both animal models and human subjects. Single injection protocols have shown the capacity to increase plasma GH levels by 2- to 10-fold for 6 days or longer, while IGF-1 levels increase by 0.5- to 3-fold for 9 to 11 days.
Growth Hormone Stimulation
The peptide functions by mimicking natural GHRH pulses while providing sustained stimulation. Research indicates that CJC-1295 stimulates GH and IGF-1 secretion, maintaining steady increases without corresponding prolactin elevation. This selective action profile distinguishes it from other growth hormone releasing compounds.
Multiple dosing protocols demonstrate cumulative effects, with IGF-1 levels remaining elevated for up to 28 days following treatment cessation.
Clinical Research and Development
Research History
ConjuChem Biotechnologies initiated CJC-1295 development during the mid-2000s with primary research objectives focused on treating visceral fat deposits in AIDS patients with lipodystrophy. The underlying hypothesis presumed that increased endogenous growth hormone levels would enhance lipolysis and improve body composition.
Clinical research demonstrated that subcutaneous administration resulted in sustained, dose-dependent increases in GH and IGF-I levels in healthy adults, with particular safety and tolerability at doses of 30 or 60 micrograms per kilogram body weight.
Clinical Trial Termination
Research progression reached phase II clinical trials before discontinuation following the death of one trial participant. The attending physician determined that the most likely explanation involved asymptomatic coronary artery disease with plaque rupture and occlusion, concluding the incident was unrelated to CJC-1295 treatment. Nevertheless, research was terminated as a precautionary measure.
Synergistic Effects with GHRP Compounds
Research protocols examining combination therapies demonstrate enhanced efficacy when CJC-1295 is administered alongside growth hormone releasing peptides (GHRPs). Studies indicate that combining GHRP-6 with CJC-1295 significantly increases GH and IGF-1 production without prolactin elevation. This synergistic relationship occurs because GHRPs create growth hormone pulses that optimize CJC-1295’s sustained release mechanism.
Comparison with Related Peptides
CJC-1295 DAC vs. Modified GRF (1-29)
Critical distinction exists between CJC-1295 with DAC and Modified GRF (1-29), often incorrectly referenced as “CJC-1295 without DAC.” These compounds share identical amino acid sequences for positions 1-29 but differ fundamentally in their C-terminus modifications.
Modified GRF (1-29) lacks the lysine extension and maleimidoproprionic acid modification, resulting in a standard 30-minute half-life comparable to natural GHRH. CJC-1295, CJC-1295 DAC, and CJC-1295 with DAC function as synonymous terms, while Modified GRF (1-29) represents a distinct peptide despite frequent misidentification in scientific literature.
Sermorelin Comparison
Sermorelin represents the natural GHRH (1-29) sequence without modifications. Both sermorelin and Modified GRF (1-29) demonstrate rapid degradation and short duration of action, while CJC-1295 with DAC provides sustained hormone elevation through its albumin-binding mechanism.
Current Status and Regulatory Considerations
Research Applications
Despite extensive research demonstrating functionality and potential therapeutic benefits, CJC-1295 remains designated exclusively for scientific research purposes. All findings and observations regarding the peptide’s functionality, mechanics, and benefits should derive exclusively from studies conducted in controlled laboratory environments.
Regulatory Status
Various regulatory bodies have established restrictions on CJC-1295 usage. The World Anti-Doping Agency (WADA) classifies growth hormone releasing factors, including CJC-1295, as prohibited substances under Section S2 of their prohibited list. Several countries, including the Netherlands, have designated non-research applications as illicit use.
Detection Methods
Advanced analytical techniques have been developed for CJC-1295 detection in biological samples. The peptide’s unique maleimido group and albumin-binding characteristics create distinctive analytical signatures that enable identification through liquid chromatography-mass spectrometry (LC-MS/MS) protocols.
Conclusion
CJC-1295 with DAC represents a significant advancement in growth hormone releasing hormone analogue development, demonstrating substantial improvements in pharmacokinetic properties through innovative bioconjugation technology. The peptide’s ability to provide sustained growth hormone elevation while maintaining physiological pulsatile patterns distinguishes it from conventional GHRH compounds.
Research applications continue to explore the peptide’s potential therapeutic applications, though clinical development was discontinued following safety concerns during phase II trials. Current regulatory frameworks restrict usage to research settings, emphasizing the need for continued scientific investigation to fully characterize the peptide’s therapeutic potential and safety profile.
The DAC technology underlying CJC-1295’s extended half-life provides a foundation for future peptide therapeutic development, demonstrating how strategic molecular modifications can transform the pharmacological properties of bioactive compounds. Understanding these mechanisms contributes to broader peptide drug development strategies and may inform future growth hormone replacement therapeutic approaches.