Chemical Name: Modified GRF 1-29, tetrasubstituted hGRF(1-29) Also Known As: Mod GRF 1-29, Modified GRF, CJC-1295 without DAC Molecular Formula: C152H252N44O42 Molecular Weight: 3368.7 g/mol Structure: Synthetic 29-amino acid analog of the N-terminal bioactive region of human growth hormone-releasing hormone (GHRH 1-44), incorporating four targeted amino acid substitutions at positions 2, 8, 15, and 27 Target: Growth hormone-releasing hormone receptor (GHRHR) on anterior pituitary somatotroph cells Category: GHRH analog / growth hormone secretagogue
Research Use Only — Disclaimer
The scientific literature on this page is provided strictly for educational and informational purposes. All Rogue Compounds products are intended for in-vitro laboratory research use only and are not approved by the FDA for human or animal consumption. The studies referenced below are independent third-party peer-reviewed publications. Rogue Compounds makes no claims that any product diagnoses, treats, cures, or prevents any disease or condition. Researchers are responsible for compliance with all applicable local, state, and federal regulations.
An Important Clarification on Naming
CJC-1295 (No DAC) is one of the most frequently mislabeled and misunderstood compounds in peptide research literature. The terminology requires careful explanation before the science can be accurately presented.
The original CJC-1295 molecule, developed by ConjuChem Biotechnologies, is technically CJC-1295 with DAC — meaning it includes a Drug Affinity Complex (DAC) modification at the C-terminus consisting of an N-epsilon-3-maleimidopropionamide derivative of lysine. This DAC modification allows the peptide to covalently bind to endogenous albumin after injection, extending its plasma half-life to approximately 6 to 8 days and enabling once-weekly dosing.
CJC-1295 without DAC — which is the compound sold and studied under that name in research settings, and the compound on this page — is technically Modified GRF 1-29, also called Mod GRF 1-29. It shares the same four tetrasubstituted amino acid positions as CJC-1295 with DAC but lacks the C-terminal lysine entirely. Without the DAC modification it does not bind to albumin, resulting in a substantially shorter half-life of approximately 30 minutes — similar to a brief but enhanced pulse of endogenous GHRH. This pharmacokinetic profile is what makes it particularly useful for research into pulsatile growth hormone secretion dynamics.
The two compounds are meaningfully different in their duration of action and pharmacokinetic behavior. Published scientific literature confirms this distinction, noting that equating the two is technically incorrect though frequently done in both commercial and some peer-reviewed contexts. Researchers designing protocols using this compound should be aware of which form they are working with.
What Is CJC-1295 (No DAC)?
CJC-1295 (No DAC), more precisely referred to as Modified GRF 1-29, is a synthetic 29-amino acid analog of the N-terminal bioactive fragment of human growth hormone-releasing hormone. Native GHRH is a 44-amino acid hypothalamic hormone that stimulates growth hormone synthesis and secretion from somatotroph cells in the anterior pituitary gland. The first 29 amino acids of GHRH — the GRF(1-29) sequence — contain the complete bioactive domain responsible for GHRHR binding and GH secretion stimulation. The remaining 15 amino acids of native GHRH contribute to receptor selectivity and plasma stability but are not required for core biological activity.
The problem with native GHRH(1-29) — also known as sermorelin — is that it is rapidly degraded in plasma by dipeptidyl peptidase-4 (DPP-4) at the N-terminus, producing a very short effective half-life of approximately 2 to 5 minutes. This rapid enzymatic degradation severely limits its utility as a research tool for studying sustained GHRH receptor signaling.
Modified GRF 1-29 was engineered with four specific amino acid substitutions to address this limitation while preserving full GHRHR binding activity and GH secretion stimulation. The substitutions are as follows.
Position 2: Alanine replaced with D-alanine. This single substitution directly blocks DPP-4 cleavage at the N-terminus, which is the primary site of enzymatic degradation in native GHRH(1-29). This substitution is the most critical modification for plasma stability.
Position 8: Asparagine replaced with glutamine. This modification reduces asparagine deamidation, which is a common chemical degradation pathway for peptides during storage and in biological fluids.
Position 15: Glycine replaced with alanine. This substitution improves resistance to oxidative degradation and contributes to enhanced molecular stability.
Position 27: Methionine replaced with leucine. This substitution eliminates susceptibility to methionine oxidation, a significant degradation pathway for peptides in aerobic environments.
Together these four substitutions extend the effective half-life of Modified GRF 1-29 to approximately 30 minutes in biological systems — significantly longer than native GHRH(1-29) but substantially shorter than CJC-1295 with DAC. This shorter half-life produces a discrete and defined pulse of GHRH receptor stimulation, making it a valuable research tool for studying physiological pulsatile GH secretion patterns.
Mechanism of Action
CJC-1295 (No DAC) binds with high affinity to the growth hormone-releasing hormone receptor (GHRHR), a class B G protein-coupled receptor expressed on somatotroph cells of the anterior pituitary gland. Binding to GHRHR activates the Gs signaling pathway through the following sequence.
GHRHR activation triggers dissociation of the associated Gs protein, releasing the alpha subunit which stimulates adenylate cyclase activity.
Adenylate cyclase converts ATP to cyclic AMP (cAMP), rapidly increasing intracellular cAMP concentration in the somatotroph.
Elevated cAMP activates protein kinase A (PKA), which phosphorylates downstream transcriptional regulators and calcium channels.
The combined effects of PKA-mediated signaling and intracellular calcium mobilization drive both the transcription of new GH mRNA and the exocytotic release of stored GH from secretory granules.
The result is an acute, pulsatile release of growth hormone from the anterior pituitary into systemic circulation. Because CJC-1295 (No DAC) has a half-life of approximately 30 minutes, this pulse is defined and time-limited, closely mimicking the physiological pattern of natural GHRH-driven GH pulsatility rather than producing the sustained continuous elevation associated with longer-acting GHRH analogs.
Downstream from the pituitary, secreted GH binds to GH receptors in the liver, stimulating IGF-1 (insulin-like growth factor 1) production. IGF-1 mediates many of the anabolic, metabolic, and tissue-repair effects associated with growth hormone axis activity in research models.
Published Research
Study 1 — Foundational Identification: CJC-1295 as a Long-Lasting GRF Analog
Authors: Jette L, Leger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP Year: 2005 Journal: Endocrinology PMID: 15817669 Full text: https://pubmed.ncbi.nlm.nih.gov/15817669/
This foundational study from ConjuChem Biotechnologies identified and characterized the CJC-1295 molecule and established the GRF receptor activation profile of the tetrasubstituted hGRF(1-29) backbone that forms the basis of CJC-1295 (No DAC). Three maleimido derivatives of hGRF(1-29) were synthesized and evaluated for GHRHR activation and pharmacokinetic stability.
The best performing compound — the tetrasubstituted form designated CJC-1295 — showed a 4-fold increase in GH area under the curve over a 2-hour period compared with native hGRF(1-29) when administered subcutaneously to normal male Sprague Dawley rats.
The compound was detectable in plasma beyond 72 hours when the DAC modification was present, with Western blot analysis confirming a CJC-1295 immunoreactive species on the serum albumin band appearing within 15 minutes of injection and remaining in circulation beyond 24 hours.
This study established the tetrasubstituted GRF(1-29) sequence as a potent and stable GHRH receptor agonist and identified CJC-1295 as the lead compound for further pharmacokinetic development. The four amino acid substitutions in the base peptide sequence — which are shared by both the DAC and no-DAC forms — were confirmed to enhance enzymatic stability and receptor affinity relative to native GHRH(1-29).
Study 2 — Human Clinical Trial: Sustained GH and IGF-1 Stimulation
Authors: Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA Year: 2006 Journal: Journal of Clinical Endocrinology and Metabolism PMID: 16352683 Full text: https://pubmed.ncbi.nlm.nih.gov/16352683/
This randomized placebo-controlled double-blind ascending dose human clinical trial examined the pharmacokinetic profile, pharmacodynamic effects, and safety of CJC-1295 (the DAC-containing form) in healthy adults aged 21 to 61 years. While this trial studied CJC-1295 with DAC, it represents the primary published human evidence base for the GH and IGF-1 stimulatory effects of the tetrasubstituted GRF(1-29) backbone shared with CJC-1295 (No DAC) and remains the foundational human pharmacodynamic reference for this class of GHRH analog. The study used two trial designs — single ascending dose over 28 days and multiple dose over 49 days.
After a single injection, dose-dependent increases in mean plasma GH concentrations of 2 to 10-fold were measured for 6 days or longer, and mean plasma IGF-1 concentrations increased 1.5 to 3-fold for 9 to 11 days.
The estimated half-life of CJC-1295 (with DAC) was 5.8 to 8.1 days, consistent with albumin binding extending the pharmacokinetic profile substantially beyond the base peptide.
After multiple doses, mean IGF-1 levels remained above baseline for up to 28 days, demonstrating a cumulative effect of repeated GHRHR stimulation on downstream IGF-1 production.
No serious adverse reactions were reported. The compound was considered safe and relatively well tolerated particularly at doses of 30 or 60 micrograms per kilogram.
The authors concluded that subcutaneous administration resulted in sustained dose-dependent increases in GH and IGF-1 and that there was evidence of cumulative effect with multiple doses, supporting the potential utility of GHRH analogs of this class as research tools and potential therapeutic agents.
Study 3 — Human Clinical Trial: Pulsatile GH Secretion Preserved
Authors: Ionescu M, Frohman LA Year: 2006 Journal: Journal of Clinical Endocrinology and Metabolism PMID: 17018654 Full text: https://pubmed.ncbi.nlm.nih.gov/17018654/
This study directly examined whether CJC-1295 administration preserved or suppressed natural pulsatile GH secretion — a critical question for understanding the physiological character of GHRH analog-driven GH release. Pulsatile GH secretion is considered important for many of the hormone’s downstream physiological effects, and non-pulsatile continuous GH elevation is associated with receptor desensitization and divergent biological outcomes. GH pulsatility was assessed by 20-minute blood sampling during an overnight 12-hour period in healthy men aged 20 to 40 years before and one week after injection of either 60 or 90 micrograms per kilogram CJC-1295.
GH secretion was significantly increased after CJC-1295 administration with pulsatility preserved. Natural GH pulse patterns were maintained rather than replaced by a continuous elevation.
Both trough GH levels and mean GH secretion increased, with the enhancement of trough GH levels identified as the primary correlate of the observed IGF-1 elevation.
IGF-1 production increased in correlation with enhanced GH secretion parameters.
The authors concluded that CJC-1295 increased trough and mean GH secretion and IGF-1 production with preserved GH pulsatility, and that long-acting GHRH preparations may have clinical utility in patients with intact pituitary GH secretory capability. The preservation of pulsatility is considered a pharmacologically favorable characteristic distinguishing GHRH analogs from direct GH administration.
Study 4 — GHRH Knockout Mouse Model: Growth Normalization
Authors: Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R Year: 2006 Journal: American Journal of Physiology — Endocrinology and Metabolism Full text: https://journals.physiology.org/doi/abs/10.1152/ajpendo.00201.2006
This preclinical study examined CJC-1295 in mice with GHRH gene ablation — the GHRH knockout (GHRHKO) mouse — which lacks endogenous GHRH and consequently displays profound GH deficiency and severely impaired growth. This model allows direct assessment of GHRH analog activity without the confounding presence of endogenous GHRH competition.
GHRHKO mice receiving daily doses of CJC-1295 exhibited normal body weight and body length compared to heterozygous controls, demonstrating complete normalization of the growth deficiency.
Mice treated every 48 and 72 hours reached higher body weight and length than placebo-treated animals, though without full growth normalization, establishing a clear frequency-dependent dose-response relationship.
Femur and tibia length remained normal in animals treated every 24 and 48 hours, confirming effects on skeletal development alongside body composition.
CJC-1295 treatment caused an increase in total pituitary RNA and GH mRNA, with immunohistochemistry confirming that proliferation of somatotroph cells had occurred — suggesting that GHRHR stimulation by CJC-1295 drove not only GH release but also expansion of the GH-secreting cell population in the anterior pituitary.
Relative lean mass and subcutaneous fat mass were normal in all treated groups.
Study 5 — GHRH Analog Class Review: Long-Acting GHRH in GH Deficiency Research
Authors: Clemmons DR Year: 2007 Journal: Hormone Research Referenced at: https://pubmed.ncbi.nlm.nih.gov/16352683/
This review article by Clemmons summarizes the preclinical and early clinical evidence for long-acting forms of growth hormone-releasing hormone including CJC-1295 and their effects in normal volunteers and adults with growth hormone deficiency. Key points relevant to CJC-1295 (No DAC) research:
Long-acting GHRH preparations tested in experimental animal models were found to extend the GH half-life and increase mean daily GH levels in a sustained manner.
Frequent sampling following administration of long-acting GHRH showed that the greatest increases occurred in trough GH levels, which increased 7.8-fold — an effect consistent with the Ionescu findings described above.
The extended GH half-life and increased trough levels resulted in increases in IGF-1 that were sustained well beyond the immediate post-injection window.
The review identifies long-acting GHRH analogs as a promising class for research into GH axis disorders and notes that their ability to stimulate endogenous GH release — rather than replacing it with exogenous GH — preserves the pulsatile character of GH secretion that is considered important for its physiological downstream effects.
An Important Distinction: CJC-1295 (No DAC) vs CJC-1295 (With DAC)
Researchers selecting between the two forms of CJC-1295 should understand the fundamental pharmacokinetic difference and its implications for study design.
CJC-1295 (No DAC) — Modified GRF 1-29 — has an approximate half-life of 30 minutes. It produces a discrete, defined pulse of GHRH receptor stimulation closely mirroring the physiological pulse of natural hypothalamic GHRH. This makes it the preferred research form for studying pulsatile GH dynamics, receptor activation kinetics, and the physiological character of natural GH axis signaling. Its short duration means it can be paired with growth hormone secretagogues such as GHRP-2, GHRP-6, or ipamorelin in research protocols where timing and receptor interaction dynamics are experimental variables.
CJC-1295 (With DAC) — the original CJC-1295 — has an approximate half-life of 6 to 8 days through albumin binding. It produces a prolonged continuous elevation of GHRH receptor stimulation. This is more appropriate for research into sustained GH and IGF-1 elevation, long-term neuroendocrine effects, or conditions such as GH deficiency where sustained receptor activation is the experimental goal.
Current Research Status
CJC-1295 with DAC entered Phase 2 clinical trials for the treatment of lipodystrophy and growth hormone deficiency but was discontinued following the death of one trial participant. The attending physician determined the most likely explanation was asymptomatic coronary artery disease with plaque rupture unrelated to the study compound, but development was terminated as a precaution. No regulatory approval was obtained for either form of CJC-1295.
CJC-1295 (No DAC) as a standalone compound has not been the subject of dedicated human clinical trials. The human pharmacodynamic data cited in this post is derived from trials of CJC-1295 with DAC, which shares the same tetrasubstituted GRF(1-29) base sequence and GHRH receptor pharmacology.
CJC-1295 (No DAC) is not approved by the FDA for any indication and is not approved for human use. It is sold and used strictly as a research compound.
The following remain unestablished in published human research specifically for the no-DAC form:
Dedicated human pharmacokinetic and pharmacodynamic data for the no-DAC form specifically.
Human safety profile for CJC-1295 (No DAC) as a standalone compound.
Long-term effects of repeated administration in any population.
Reconstitution Note
CJC-1295 (No DAC) is a peptide compound. Bacteriostatic water is the standard reconstitution solvent for this compound in laboratory research settings. It dissolves readily in bacteriostatic water without requiring acidic solvents. Always confirm the recommended solvent against the specific lot datasheet before reconstitution.
In-Use Period and Storage
Before Reconstitution — Lyophilized Powder
Rogue Compounds stores all products refrigerated prior to shipping to maintain compound integrity from production through to delivery. Upon receipt researchers should store vials at 2 to 8 degrees Celsius immediately. Keep vials sealed, dry, and away from direct light until ready for use. Do not freeze. Repeated freeze-thaw cycling has been documented in peer-reviewed pharmaceutical formulation literature to accelerate structural degradation even in dry powder form, potentially compromising molecular integrity and experimental reproducibility.
Why We Refrigerate Instead of Freeze
Freezing and thawing introduces mechanical and osmotic stress at the molecular level. Published pharmaceutical research identifies freeze-thaw cycling as a significant risk factor for loss of structural integrity in peptides and protein-based compounds. To protect compound quality at every stage of handling and fulfillment, Rogue Compounds maintains refrigerated rather than frozen cold chain storage throughout the entire process.
After Reconstitution — Liquid Solution
Store reconstituted solutions refrigerated at 2 to 8 degrees Celsius immediately after preparation. Protect from light at all stages of storage and handling. Avoid repeated freeze-thaw cycles of reconstituted solutions regardless of the diluent used. Use within the timeframe recommended for the individual compound. Label each aliquot with the compound name, concentration, date of reconstitution, and diluent used. Discard any solution that shows visible particulate matter, discoloration, or signs of contamination.
Note: Storage and in-use recommendations on this page are provided as general laboratory guidance based on standard peptide handling practices documented in peer-reviewed pharmaceutical literature. Researchers should always refer to the individual compound’s published research literature and datasheet for any specific requirements. All products sold by Rogue Compounds are intended strictly for in-vitro laboratory research use only.
Available from Rogue Compounds
View the CJC-1295 (No DAC) product page: https://roguecompounds.com/product/cjc-1295-no-dac/