Research Comparison

CJC-1295 With DAC vs Without DAC: Sustained vs Pulsatile GH Release

CJC-1295 exists in two distinct forms that produce dramatically different pharmacokinetic profiles despite sharing the same core peptide sequence: the DAC (Drug Affinity Complex) version and the non-DAC version, commonly known as Mod GRF 1-29 or Modified Growth Hormone Releasing Factor. Both are synthetic analogs of growth hormone-releasing hormone (GHRH) that stimulate the anterior pituitary to release growth hormone. However, the presence or absence of the DAC modification creates a fundamental divergence in how growth hormone is released. The DAC version binds to serum albumin and produces sustained, continuously elevated GH levels over days, while the non-DAC version is rapidly cleared and produces acute, physiological-style GH pulses that closely mimic the body's natural secretory pattern. For researchers studying somatotropic axis physiology, this distinction has profound implications for experimental design, as the pattern of GH release is often as biologically significant as the total amount released.

Side-by-Side Comparison

Property	CJC-1295 With DAC	CJC-1295 Without DAC (Mod GRF 1-29)
Half-Life	Approximately 6-8 days (extended by albumin binding)	Approximately 30 minutes (rapid clearance)
GH Release Pattern	Sustained, continuously elevated baseline GH levels	Acute pulsatile release that mimics natural physiological GH secretion
DAC Function	Maleimidopropionic acid (MPA) moiety covalently binds to serum albumin, preventing renal clearance	No albumin binding modification; subject to standard rapid peptide clearance
Administration Frequency	1-2 times per week (due to extended half-life)	Multiple times daily (due to rapid 30-minute half-life)
Physiological Mimicry	Non-physiological: produces constant elevated GH baseline without normal pulsatility	Physiological: produces discrete GH pulses that replicate natural ultradian rhythm

The DAC Modification Explained: Albumin Binding and Pharmacokinetic Consequences

The Drug Affinity Complex (DAC) is a maleimidopropionic acid (MPA) moiety attached to a reactive lysine residue on the CJC-1295 peptide chain. This chemical modification is specifically engineered to form a covalent bond with Cysteine-34 on human serum albumin after subcutaneous injection. Albumin is the most abundant protein in blood plasma, with a half-life of approximately 19-21 days, and by hitching a ride on this long-lived carrier protein, DAC-modified CJC-1295 effectively borrows albumin's pharmacokinetic profile. The result is a half-life extension from approximately 30 minutes (the clearance rate of the unmodified peptide) to approximately 6-8 days, representing a roughly 300-fold increase in circulating persistence. This albumin-binding strategy has been validated as a general principle in pharmacology and is used in other long-acting peptide therapeutics. The pharmacokinetic consequences of this modification are profound and extend far beyond simple convenience of less frequent dosing. CJC-1295 with DAC produces a fundamentally different pattern of growth hormone stimulation. Because the peptide remains continuously present in circulation for days, it provides constant stimulation to GHRH receptors on somatotroph cells in the anterior pituitary. This results in a tonically elevated GH baseline, a sustained plateau rather than the discrete peaks and troughs that characterize natural GH secretion. Research in healthy subjects has demonstrated that CJC-1295 with DAC can elevate mean GH levels by 2-10 fold and IGF-1 levels by 1.5-3 fold over baseline, with these elevations persisting for days after a single injection. By contrast, CJC-1295 without DAC (Mod GRF 1-29) is cleared rapidly, producing a sharp but transient spike in GH release that resolves within 1-2 hours. This acute pulsatile pattern closely mirrors the natural ultradian rhythm of GH secretion, where the pituitary releases GH in discrete bursts approximately every 3-4 hours, with the largest pulse occurring during slow-wave sleep. The biological significance of pulsatile versus sustained GH exposure is well documented: hepatic GH receptors exhibit different signaling responses to pulsatile versus continuous GH exposure, with pulsatility being important for sexually dimorphic gene expression patterns, optimal IGF-1 production, and proper lipolytic signaling. Researchers interested in studying GH physiology under conditions that preserve normal pulsatility should favor the non-DAC version, while those interested in maximal sustained GH/IGF-1 elevation may prefer the DAC-modified form.

Frequently Asked Questions

What is DAC in CJC-1295 with DAC?▼

DAC stands for Drug Affinity Complex, which is a maleimidopropionic acid (MPA) chemical moiety attached to the CJC-1295 peptide. After subcutaneous injection, this MPA group forms a covalent bond with Cysteine-34 on human serum albumin, the most abundant protein in blood plasma. By binding to albumin (which has a natural half-life of approximately 19-21 days), the CJC-1295 peptide is protected from normal renal clearance and enzymatic degradation, extending its effective half-life from approximately 30 minutes to approximately 6-8 days. This allows continuous GHRH receptor stimulation and sustained GH elevation from infrequent dosing.

Which version of CJC-1295 produces a more physiological GH release pattern?▼

CJC-1295 without DAC (Mod GRF 1-29) produces a GH release pattern that more closely mimics natural physiology. Due to its rapid 30-minute half-life, it creates discrete, acute GH pulses that replicate the body's natural ultradian GH secretory rhythm of bursts every 3-4 hours. CJC-1295 with DAC, by contrast, produces a sustained, continuously elevated GH baseline due to its 6-8 day half-life from albumin binding. This non-physiological constant stimulation differs substantially from natural pulsatile GH secretion. Research indicates that GH pulsatility is biologically significant for hepatic signaling, sexually dimorphic gene expression, and optimal IGF-1 regulation, making the non-DAC version preferable for studies requiring physiological GH kinetics.