CJC-1295 with DAC: A Long-Acting GHRH Analogue with Drug Affinity Complex

Research summary. CJC-1295 is a synthetic analogue of growth hormone-releasing hormone (GHRH) modified to extend its plasma half-life from minutes to days through covalent attachment to serum albumin. The "DAC" (Drug Affinity Complex) variant carries a maleimidopropionic acid linker that reacts irreversibly with cysteine-34 of circulating albumin, creating a long-acting depot that releases the active peptide on a timescale measured in days rather than minutes.

Molecular profile

• Class: Long-acting GHRH analogue (1–29 fragment with stabilising substitutions and DAC linker)
• Core sequence (residues 1–29 with substitutions): 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
• Approximate molecular weight: ~3367 g/mol (with DAC linker)
• PubChem CID: 56841945

The peptide builds on Mod GRF 1-29 (also known as CJC-1295 No DAC), itself a stabilised version of the first 29 residues of human GHRH with four amino-acid substitutions to resist enzymatic degradation. The DAC variant adds a maleimide linker at the C-terminus that conjugates to a cysteine residue on circulating human serum albumin, dramatically extending the molecule's half-life.

Mechanism of action

CJC-1295 DAC engages the GHRH receptor on somatotroph cells of the anterior pituitary, triggering Gαs-mediated cAMP signalling and stimulating synthesis and secretion of growth hormone. The receptor pharmacology is essentially that of native GHRH; the engineering is in the pharmacokinetics.

The strategic intent of the DAC modification is to maintain elevated baseline GHRH-receptor stimulation while preserving the natural pulsatility of GH secretion driven by hypothalamic somatostatin tone. This contrasts with continuous GH administration, which suppresses endogenous regulation. Whether full preservation of physiological pulsatility is actually achieved in practice is debated in the literature.

Preclinical and clinical research highlights

Foundational pharmacokinetic study. The seminal characterisation of CJC-1295 DAC (Teichman et al., 2006) reported that single subcutaneous administration to healthy adults produced sustained elevations in mean GH and IGF-1 concentrations lasting approximately 6–8 days. Multiple-dose studies showed dose-dependent increases in IGF-1 with a plateau at higher doses, consistent with negative feedback regulation [1].

Comparison with shorter-acting GHRH analogues. Sermorelin (the unmodified GHRH 1-29 fragment) has an in-vivo half-life of approximately 10–20 minutes. Mod GRF 1-29 (CJC-1295 No DAC) has a half-life of approximately 30 minutes. CJC-1295 DAC has a half-life of approximately 6–8 days. This thousand-fold extension is the principal pharmacological feature of the DAC variant.

IGF-1 dose-response. Across reported studies, CJC-1295 DAC dose escalation produces a corresponding increase in steady-state IGF-1, which has been a primary biomarker for studying chronic GHRH-receptor stimulation in healthy adult research subjects.

Safety signal in early trials. Clinical development of CJC-1295 DAC was paused in the late 2000s following a fatality reported during a clinical trial; the causal relationship to study drug was disputed but contributed to the molecule's transition out of formal pharmaceutical development. The compound remains widely studied in academic and research-peptide contexts.

Position within the GH-secretagogue landscape

CJC-1295 DAC represents one half of a common research strategy: pairing a long-acting GHRH analogue with a short-acting growth hormone-releasing peptide (GHRP) such as ipamorelin, GHRP-2, or GHRP-6. The two classes activate distinct receptor systems — GHRH receptor versus the ghrelin/GHS-R1a receptor — and produce greater GH secretion in combination than either alone. This combinatorial pharmacology has been a workhorse of preclinical GH-axis research for two decades.

Current research status

CJC-1295 DAC remains an investigational research peptide. It is not approved as a therapeutic by any major regulatory authority and is listed by the World Anti-Doping Agency as a prohibited substance under category S2 (peptide hormones, growth factors, related substances and mimetics). Its principal research applications are:

• Studies of GHRH-receptor pharmacology and chronic dosing kinetics
• Investigation of GH-axis regulation under sustained vs. pulsatile receptor engagement
• Combination studies with GHRP-class molecules
• Reference compound for development of newer long-acting GHRH analogues

Key takeaways for researchers

• CJC-1295 DAC is a long-acting GHRH analogue (1–29 fragment) modified with a maleimide linker that conjugates irreversibly to circulating albumin.
• Its half-life of ~6–8 days is dramatically longer than that of native GHRH (~10 min) or non-DAC variants (~30 min).
• It produces sustained elevation of GH and IGF-1 in research subjects rather than pulsatile peaks.
• It is on the WADA Prohibited List and is not an approved therapeutic.

References

1. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. Journal of Clinical Endocrinology and Metabolism. 2006;91(3):799–805.

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This article is provided for educational and research purposes only. CJC-1295 DAC is an investigational research peptide. It is not an approved drug or therapeutic agent and is not intended for human consumption, diagnosis, treatment, cure, or prevention of any disease or condition. CJC-1295 is listed by the World Anti-Doping Agency as a prohibited substance. All work involving this peptide should be conducted by qualified personnel within an appropriate research setting and in compliance with applicable institutional and regulatory requirements.