CJC-1295 No DAC (Modified GRF 1-29) Research Guide

CJC-1295 without DAC, commonly known as Modified GRF(1-29) or Mod GRF(1-29), is a synthetic analog of growth hormone-releasing hormone (GHRH) that has become one of the most widely studied peptides in neuroendocrine research. While it shares a name with its longer-acting sibling CJC-1295 with DAC, the two compounds have fundamentally different pharmacokinetic profiles and research applications. This guide provides a thorough examination of CJC-1295 No DAC as a standalone compound, drawing from published literature to detail its mechanism of action, structural modifications, half-life characteristics, and the research that distinguishes it from other GHRH analogs.

What Is CJC-1295 No DAC (Modified GRF 1-29)?

To understand CJC-1295 No DAC, you need to start with the parent molecule: growth hormone-releasing hormone (GHRH). Endogenous GHRH is a 44-amino acid peptide produced by the hypothalamus that acts on GHRH receptors (GHRH-R) on somatotroph cells in the anterior pituitary gland to stimulate the synthesis and secretion of growth hormone (GH). Early research established that the first 29 amino acids of GHRH (known as GRF 1-29 or sermorelin) contain the full biological activity needed for receptor binding and activation.

However, native GRF(1-29) has a critical limitation: it is rapidly degraded in the bloodstream by the enzyme dipeptidyl peptidase-IV (DPP-IV), which cleaves the peptide at the alanine-2 position. This gives native GRF(1-29) an extremely short plasma half-life of approximately 5-7 minutes, making it impractical for many research applications.

CJC-1295 No DAC addresses this problem through four specific amino acid substitutions at positions 2, 8, 15, and 27 of the GRF(1-29) sequence. These tetra-substitutions were engineered to resist DPP-IV cleavage while preserving full biological activity at the GHRH receptor. The result is a modified peptide with a plasma half-life of approximately 30 minutes — roughly 4 to 6 times longer than native GRF(1-29), though still much shorter than CJC-1295 with DAC.

The Four Key Amino Acid Substitutions

Position	Native GRF(1-29)	Mod GRF(1-29) / CJC-1295 No DAC	Purpose
2	Alanine (Ala)	D-Alanine (D-Ala)	DPP-IV resistance (primary cleavage site)
8	Asparagine (Asn)	Glutamine (Gln)	Reduces deamidation; improves stability
15	Glycine (Gly)	Alanine (Ala)	Enhanced helical stability and receptor binding
27	Methionine (Met)	Leucine (Leu)	Prevents methionine oxidation

Each substitution addresses a specific vulnerability in the native peptide sequence. The D-alanine at position 2 is the most critical, as it directly blocks the DPP-IV cleavage site that destroys native GHRH activity within minutes. The leucine-for-methionine swap at position 27 eliminates a major oxidation hotspot that would otherwise reduce shelf stability and complicate storage. For detailed guidance on peptide storage, see our article on how to store peptides properly.

CJC-1295 No DAC vs. CJC-1295 with DAC: A Critical Distinction

This is where the naming convention creates the most confusion. “CJC-1295” was originally developed by ConjuChem Biotechnologies (now part of ConjuChem LLC) as a long-acting GHRH analog designed for once-weekly or less-frequent dosing. The “CJC-1295” in its original form includes a Drug Affinity Complex (DAC) — a maleimide-derivative lysine residue appended to the C-terminus of the tetra-substituted GRF(1-29) sequence. This DAC moiety reacts with serum albumin after subcutaneous injection, forming a covalent bond that dramatically extends the peptide’s plasma half-life.

Half-Life Comparison

Compound	Approximate Half-Life	GH Elevation Duration	Mechanism
Native GRF(1-29) / Sermorelin	5-7 minutes	~1 hour	Native GHRH fragment; rapidly degraded by DPP-IV
CJC-1295 No DAC (Mod GRF 1-29)	~30 minutes	~2-3 hours	Tetra-substituted GRF(1-29); DPP-IV resistant
CJC-1295 with DAC	5.8-8.1 days	6-10+ days	Albumin-conjugating DAC; sustained release

The implications of this difference are profound for research design. CJC-1295 No DAC produces discrete, pulsatile GH release events that more closely mimic the natural pattern of endogenous GHRH signaling. Each administration triggers a GH pulse that peaks within 30-60 minutes and returns to baseline within 2-3 hours. CJC-1295 with DAC, by contrast, produces sustained GH elevation over days, with research by Teichman et al. (2006) demonstrating 2- to 10-fold increases in mean plasma GH concentrations persisting for 6 or more days after a single injection in healthy adults.

Mechanism of Action

GHRH Receptor Signaling

CJC-1295 No DAC acts as an agonist at the GHRH receptor (GHRH-R), a Class B G-protein coupled receptor (GPCR) expressed primarily on somatotroph cells of the anterior pituitary gland. Upon binding, the activated GHRH-R couples to the stimulatory G-protein (Gs), which activates adenylyl cyclase. This generates cyclic adenosine monophosphate (cAMP), which in turn activates protein kinase A (PKA). The PKA-dependent signaling cascade leads to:

1. GH gene transcription: PKA phosphorylates the transcription factor CREB (cAMP response element-binding protein), which binds to cAMP response elements in the GH gene promoter, stimulating new GH synthesis.
2. GH vesicle exocytosis: PKA-dependent calcium channel activation increases intracellular calcium, triggering the release of stored GH vesicles.
3. Somatotroph proliferation: Chronic GHRH-R activation promotes the growth and division of somatotroph cells, increasing the pituitary’s capacity for GH production over time.

Synergy with GH Secretagogues

The GHRH-R signaling pathway (cAMP/PKA) is mechanistically distinct from the GHS-R1a pathway (phospholipase C/calcium) activated by ghrelin-mimetic peptides. This creates a well-documented synergy when GHRH analogs are combined with GH secretagogues. CJC-1295 No DAC activates the “volume” of GH production through cAMP, while a GHS like ipamorelin provides the complementary “trigger” through calcium signaling. The result is a GH pulse substantially larger than either agent produces alone.

This synergy is the basis for the widely studied CJC-1295/Ipamorelin combination. For a detailed examination of this pairing, see our CJC-1295/Ipamorelin research guide.

Pharmacokinetic and Pharmacodynamic Profile

GH Response Characteristics

When CJC-1295 No DAC is administered subcutaneously, it produces a rapid-onset GH pulse with the following general characteristics observed in research settings:

• Onset: GH levels begin to rise within 5-15 minutes of subcutaneous injection.
• Peak: Maximum GH concentration typically occurs at 30-60 minutes post-administration.
• Duration: Elevated GH levels persist for approximately 2-3 hours before returning to baseline.
• Pulsatile pattern: The discrete pulse-and-return pattern mimics endogenous GHRH signaling and is considered favorable for preserving the normal negative feedback regulation of the GH axis.

This pharmacodynamic profile contrasts sharply with CJC-1295 with DAC, where Ionescu and Frohman (2006) demonstrated that pulsatile GH secretion persists even during continuous CJC-1295 DAC stimulation, though mean GH levels remain elevated for days. This study, published in the Journal of Clinical Endocrinology and Metabolism, was significant because it showed that the pituitary’s inherent pulsatile rhythm is not overridden by sustained GHRH-R stimulation.

IGF-1 Response

GH stimulates the liver to produce insulin-like growth factor 1 (IGF-1), which mediates many of GH’s downstream effects on growth, metabolism, and tissue repair. Research on CJC-1295 (both with and without DAC) has demonstrated dose-dependent increases in circulating IGF-1 levels. Teichman et al. (2006) reported 1.5- to 3-fold increases in mean plasma IGF-1 concentrations persisting for 9-11 days after a single injection of CJC-1295 with DAC in healthy adults. For CJC-1295 No DAC, IGF-1 elevations are more modest and transient due to the shorter half-life, but repeated pulsatile administration has been shown to produce sustained IGF-1 increases in research protocols.

Development History: From GRF(1-29) to Mod GRF(1-29)

The development of CJC-1295 No DAC follows a logical progression through GHRH analog research:

1. 1982: Endogenous GHRH is first isolated and characterized from pancreatic tumors by Guillemin and Rivier (independently). The 44-amino acid sequence is identified.
2. 1980s-1990s: Researchers determine that the first 29 amino acids (GRF 1-29) retain full biological activity. This fragment becomes known as sermorelin and is later developed clinically. For more on sermorelin, see our sermorelin research guide.
3. 1990s: Multiple groups work on GHRH analogs with improved metabolic stability. The critical role of DPP-IV in GHRH degradation is established, making position 2 modifications a primary focus.
4. 2005: Jette et al. publish the seminal paper identifying CJC-1295 as a long-lasting GRF analog through albumin bioconjugation (DAC technology). The tetra-substituted GRF(1-29) base sequence is characterized, showing a 4-fold increase in GH AUC compared to native GRF(1-29) in rats even without the DAC moiety.
5. 2006: Teichman et al. publish the first human PK/PD data for CJC-1295 with DAC, establishing its 5.8-8.1 day half-life and demonstrating sustained GH/IGF-1 elevation.
6. 2006: Ionescu and Frohman demonstrate that pulsatile GH secretion is maintained during continuous CJC-1295 DAC stimulation, providing important physiological insights.

The “No DAC” version entered the research landscape as the base peptide — the tetra-substituted GRF(1-29) without the albumin-binding DAC moiety. While ConjuChem’s clinical development focused on the DAC version for its convenience of less-frequent dosing, the No DAC version gained traction in the research community specifically because its shorter half-life produces pulsatile GH release patterns considered more physiologically relevant.

Research Applications

Neuroendocrine Physiology

CJC-1295 No DAC serves as a valuable research tool for studying GHRH-R signaling, somatotroph function, and the regulation of the GH/IGF-1 axis. Its improved stability compared to native GHRH makes it more practical for experimental protocols, while its short half-life allows researchers to deliver discrete GHRH-R stimulation events and study the resulting GH pulse dynamics without the confounding sustained elevation produced by the DAC version.

Combination Studies with GH Secretagogues

As discussed above, the combination of CJC-1295 No DAC with GHS-R1a agonists represents one of its primary research applications. The most common pairings studied include:

• CJC-1295 No DAC + Ipamorelin: The most widely studied combination, leveraging the clean selectivity profile of ipamorelin (no ACTH/cortisol effects) with the GHRH-R activation of CJC-1295 No DAC.
• CJC-1295 No DAC + GHRP-2: Studied for maximum GH output, though GHRP-2 does stimulate some cortisol and prolactin release.
• CJC-1295 No DAC + GHRP-6: An earlier combination studied before ipamorelin’s selectivity made it the preferred partner. GHRP-6 produces significant appetite stimulation through its broader receptor activity.

Aging and GH Decline Research

Age-related decline in GH secretion (somatopause) is a well-documented phenomenon. Research has explored whether GHRH analogs can restore youthful GH pulsatility in aging models. A landmark 1992 study by Corpas et al. demonstrated that twice-daily subcutaneous GRF(1-29) administration reversed the age-related decline in GH and IGF-1 levels in older men, establishing the principle that the aging pituitary retains the capacity to respond to GHRH stimulation. CJC-1295 No DAC, with its improved stability, represents a refined tool for this line of investigation.

Metabolic Research

The GH/IGF-1 axis plays important roles in lipid metabolism, glucose homeostasis, and body composition. Research has examined how pulsatile GHRH-R stimulation affects these metabolic parameters. Alba et al. (2006) showed that once-daily CJC-1295 (DAC version) normalized growth in GHRH knockout mice, providing proof of concept that synthetic GHRH-R agonists can fully substitute for endogenous GHRH in a research model. While this study used the DAC version, the findings are relevant to understanding GHRH-R signaling more broadly.

Dosing Parameters in Published Research

The following table summarizes dosing protocols described in published research involving CJC-1295 (both versions) and its precursor GRF(1-29). These are provided solely as reference to the published literature.

Study	Compound	Model	Route	Dose	Frequency	Key Finding
Corpas et al. (1992)	GRF(1-29)	Elderly men	SC	1 mg/day	Twice daily	Reversed age-related GH/IGF-1 decline
Jette et al. (2005)	CJC-1295 (DAC)	Rats	SC	Variable	Single dose	4-fold GH AUC increase vs native GRF(1-29)
Teichman et al. (2006)	CJC-1295 (DAC)	Healthy adults	SC	30-60 mcg/kg	Single or weekly	2-10x GH increase for 6+ days; t1/2 5.8-8.1 days
Ionescu & Frohman (2006)	CJC-1295 (DAC)	Healthy adults	SC	60 mcg/kg	Weekly x 3	Pulsatile GH secretion preserved during sustained GHRH-R stimulation
Alba et al. (2006)	CJC-1295 (DAC)	GHRH-KO mice	SC	Variable	Once daily	Normalized growth in GHRH-deficient model

Comparison with Other GHRH Analogs

Parameter	Sermorelin (GRF 1-29)	CJC-1295 No DAC (Mod GRF 1-29)	CJC-1295 with DAC	Tesamorelin
Structure	Native GRF(1-29)	Tetra-substituted GRF(1-29)	Tetra-sub GRF(1-29) + DAC	Trans-3-hexenoic acid-GRF(1-44)
Half-life	5-7 min	~30 min	5.8-8.1 days	26-38 min
GH release pattern	Brief pulse	Moderate pulse	Sustained elevation	Moderate pulse
DPP-IV resistance	None	High	High + albumin binding	Moderate
Clinical development	FDA-approved (discontinued)	Research only	Phase 2 completed	FDA-approved

For more on sermorelin, see our sermorelin research guide. For tesamorelin, see our tesamorelin research guide.

Safety Considerations in Published Research

The safety data available for CJC-1295 primarily comes from studies of the DAC version, which progressed further in clinical development. Teichman et al. (2006) reported that CJC-1295 with DAC was “safe and relatively well tolerated” in healthy adults at doses of 30 or 60 mcg/kg, with the most common adverse events being injection site reactions (erythema, swelling, pain) that were generally mild and transient.

The Alba et al. (2006) study in GHRH-KO mice noted that CJC-1295 DAC treatment normalized the GH/IGF-1 axis without observed toxicity over the treatment period. Ionescu and Frohman (2006) confirmed that three weekly doses of 60 mcg/kg CJC-1295 DAC in healthy adults maintained pulsatile GH secretion without tachyphylaxis or loss of response, suggesting the pituitary does not rapidly desensitize to sustained GHRH-R activation.

Fewer published safety data exist specifically for CJC-1295 No DAC, though its shorter half-life and resulting lower cumulative GHRH-R exposure per dose would be expected to carry a comparable or lower risk profile. The absence of the DAC moiety also eliminates any theoretical concerns related to albumin conjugation and its potential immunogenic effects.

Storage and Handling

CJC-1295 No DAC should be stored lyophilized at -20°C for long-term stability. The leucine substitution at position 27 (replacing methionine) significantly improves oxidative stability compared to native GRF(1-29). Once reconstituted in bacteriostatic water, store at 2-8°C and use within 2-4 weeks. Aliquoting before freezing is recommended for reconstituted solutions to avoid degradation from freeze-thaw cycles.

CJC-1295 No DAC is available for research purposes at NorthPeptide.

Summary of Key Research References

Study	Year	Type	Focus	Reference
Corpas et al.	1992	Clinical	Twice-daily GRF(1-29) reversed age-related GH/IGF-1 decline in elderly men	PMID 1379256
Jette et al.	2005	Preclinical	Identification of CJC-1295 as long-lasting GRF analog via albumin bioconjugation; 4x GH AUC vs native GRF(1-29)	PMID 15817669
Teichman et al.	2006	Clinical (Phase 1/2)	PK/PD of CJC-1295 with DAC in healthy adults; 5.8-8.1 day half-life; 2-10x GH increase	PMID 16352683
Ionescu & Frohman	2006	Clinical	Pulsatile GH secretion maintained during continuous CJC-1295 DAC stimulation	PMID 17018654
Alba et al.	2006	Preclinical	Daily CJC-1295 normalized growth in GHRH knockout mice	PMID 16822960
Iovino et al.	2010	Review	Chemical modification of GHRH analogs for neuroendocrine therapy	PMC2815023
Sigalos & Pastuszak	2017	Review	Safety and efficacy review of growth hormone secretagogues including GHRH analogs	PMC5632578
Sinha et al.	2020	Review	Role of GH secretagogues in body composition management	PMC7108996

Written by NorthPeptide Research Team

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This article is intended solely as a summary of published scientific research. It does not constitute medical advice, treatment recommendations, or an endorsement for any therapeutic purpose. The research discussed herein is predominantly preclinical, and results may not translate to human outcomes. Researchers should consult relevant institutional review boards and regulatory guidelines before designing studies involving these compounds.

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