CJC-1295 with DAC: Research Overview

CJC-1295 with DAC is a synthetic growth hormone-releasing hormone (GHRH) analog engineered by ConjuChem Biotechnologies to overcome the principal limitation of native GHRH: an in vivo half-life of only a few minutes. By attaching a drug affinity complex (DAC) that covalently binds circulating albumin, the molecule extends its functional half-life to approximately 6–8 days in humans. A single randomized, placebo-controlled pharmacokinetic study published in 2006 remains the primary human evidence base for this compound, providing dose-response data on growth hormone (GH) and insulin-like growth factor-1 (IGF-1) elevations after subcutaneous injection. The compound is classified as a research chemical worldwide and is not approved for human therapeutic use.

What is CJC-1295 with DAC?

CJC-1295 with DAC is a 30-amino-acid modified GHRH analog (based on GRF 1-29) with a molecular weight of approximately 4541 Da. The key structural feature is the drug affinity complex — a maleimidoproprionic acid-lysine linker that reacts with the free thiol group of cysteine-34 on serum albumin following injection, forming a covalent bond. This albumin conjugation dramatically prolongs circulating half-life compared to the parent peptide. CJC-1295 without DAC (also marketed as Modified GRF 1-29 or Mod-GRF) retains only four amino acid substitutions that confer protease resistance but does not carry the albumin-binding linker, giving it a plasma half-life of roughly 30 minutes. The two are distinct compounds with fundamentally different pharmacokinetic profiles; only the DAC form has published human PK data from a controlled trial.

Mechanism of Action

CJC-1295 with DAC binds and activates the GHRH receptor (GHRHR) on somatotroph cells of the anterior pituitary gland. Receptor engagement activates adenylyl cyclase via Gs protein coupling, raising intracellular cyclic AMP (cAMP), which in turn activates protein kinase A and triggers calcium influx. The net result is both synthesis and pulsatile secretion of growth hormone. Because the DAC linker keeps the peptide anchored to albumin in the circulation, receptor stimulation is prolonged and relatively sustained rather than the brief pulse that would follow injection of native GHRH.

Downstream, elevated GH stimulates hepatic production of IGF-1, which mediates many of the downstream anabolic and tissue-maintenance effects attributed to the GH/IGF-1 axis. Because CJC-1295 with DAC acts upstream at the GHRH receptor rather than as a direct GH replacement, it preserves the feedback sensitivity of the pituitary-GH axis, including somatostatin-mediated inhibition. This is a pharmacologically important distinction from exogenous recombinant GH administration.

What the Research Shows

The primary human evidence base is a randomized, double-blind, placebo-controlled, ascending-dose study by Teichman et al. published in the Journal of Clinical Endocrinology and Metabolism in 2006 (PMID 16352683). The study enrolled healthy adults who received single subcutaneous doses or multiple doses of CJC-1295 (the DAC form). The authors observed dose-dependent, sustained elevations in both mean GH and IGF-1 levels. Mean GH area-under-the-curve increased significantly over placebo, with GH elevations persisting for up to 6 days after a single injection. IGF-1 elevations of 1.5- to 3-fold above baseline were maintained throughout the observation window. No serious adverse events were reported; mild injection-site reactions were the most common finding.

A companion study in the GHRH-knockout mouse model (Ionescu & Frohman, AJP-Endo, 2006) demonstrated that once-daily CJC-1295 normalized growth in GHRH-deficient animals, confirming that the pharmacological effect is mediated specifically through GHRHR agonism. No phase 2 or phase 3 clinical trials evaluating efficacy endpoints in patient populations have been published for CJC-1295 with DAC.

Pharmacokinetics

Following subcutaneous injection, CJC-1295 with DAC undergoes rapid albumin conjugation at the injection site and in plasma, resulting in an effective half-life of approximately 6–8 days — mirroring the 19-day half-life of serum albumin in proportion to the kinetics of the covalent bond and peptide degradation. Peak plasma concentrations are reached within 1–4 hours post-injection. The long half-life allows for once-weekly or once-biweekly subcutaneous administration in research protocols while maintaining supraphysiological GH pulsatility. Clearance is principally through proteolytic degradation of the albumin-peptide conjugate.

Common Research Dose Ranges

Not medical advice. These are ranges reported in research literature, not personalized recommendations. Consult your physician.

The Teichman et al. 2006 study (PMID 16352683) evaluated subcutaneous doses in the range of approximately 30–120 mcg in healthy adults, with literature reporting once-weekly or once-biweekly administration. This remains the sole published controlled human pharmacokinetic study for CJC-1295 with DAC. Dose ranges for the non-DAC form (CJC-1295 without DAC / Mod-GRF 1-29) are distinct and not addressed here.

Storage

Lyophilized CJC-1295 with DAC should be stored at −20 °C in a desiccated, light-protected environment. Once reconstituted with bacteriostatic water, the solution should be kept at 2–8 °C and used within 28 days. The DAC linker is stable at these storage temperatures; excessive heat or freeze-thaw cycles can impair the reactive maleimide group and reduce albumin-binding efficiency.

What CJC-1295 with DAC Is NOT

CJC-1295 with DAC is not the same compound as CJC-1295 without DAC (Mod-GRF 1-29). Despite sharing a very similar base peptide sequence, the absence of the albumin-binding DAC linker in the no-DAC form results in a plasma half-life of approximately 30 minutes versus 6–8 days for the DAC form. Research protocols, dosing intervals, and PK profiles differ substantially between the two. The only published human controlled trial (Teichman 2006) applies exclusively to the DAC form. CJC-1295 with DAC is also not a growth hormone replacement; it is a GHRH receptor agonist that stimulates the pituitary to secrete endogenous GH rather than supplying exogenous GH directly.

References

Citations for this guide are listed below. All PubMed links resolve to the NCBI abstract page for the referenced article.