CJC-1295 w/ DAC

CJC-1295 with DAC is a synthetic GHRH (growth hormone-releasing hormone) analog conjugated with a Drug Affinity Complex (DAC) that enables covalent binding to serum albumin. Developed by ConjuChem Biotechnologies, this modification extends the peptide’s half-life from minutes to approximately 6-8 days, allowing for sustained GHRH receptor activation. The DAC technology uses a reactive maleimidopropionyl group linked to the peptide’s lysine residue (position 30), which forms a covalent thioether bond with Cys34 on circulating albumin after subcutaneous injection. This albumin conjugation protects the peptide from proteolytic degradation and renal clearance. CJC-1295 with DAC produces a continuous rather than pulsatile elevation of growth hormone levels, distinguishing it pharmacologically from the non-DAC version. It has been investigated in clinical pharmacokinetic studies characterizing its extended duration of action.

CJC-1295 with DAC has been investigated for its sustained activation of the GHRH receptor through albumin-protected delivery. Upon subcutaneous injection, the maleimidopropionyl-DAC moiety reacts with Cys34 on circulating albumin, forming a stable covalent conjugate. This albumin-bound form maintains GHRHR agonist activity while being shielded from DPP-IV cleavage and renal filtration. Researchers observed that the resulting sustained GHRHR activation produces a continuous elevation of GH and IGF-1 levels rather than the pulsatile pattern seen with non-DAC analogs. Studies suggest that continuous GHRHR stimulation may lead to different downstream signaling dynamics compared to pulsatile stimulation, including potential receptor desensitization effects. In clinical pharmacokinetic studies, researchers observed that a single injection of CJC-1295 with DAC was associated with elevated GH and IGF-1 levels persisting for 6-14 days, demonstrating the extended pharmacokinetic profile conferred by the DAC technology.

Clinical Pharmacokinetics

Teichman et al. (2006) investigated CJC-1295 (DAC:GRF) in a dose-escalation clinical study. Researchers observed dose-dependent increases in GH and IGF-1 levels that persisted for 6-14 days after a single subcutaneous injection, confirming the extended half-life of the albumin-conjugated peptide [1].

DAC Technology

Bhatt et al. (2003) described the Drug Affinity Complex technology for extending peptide half-life through albumin conjugation. The study characterized the chemical kinetics of the maleimide-thiol reaction with serum albumin and the resulting pharmacokinetic improvements [2].

GHRH Analog Development

Ionescu M, Bhatt DL (2005) reviewed the development of long-acting GHRH analogs including CJC-1295, describing the rationale for sustained versus pulsatile GHRH receptor activation and the potential implications for GH axis physiology [3].