CJC-1295 No DAC

CJC-1295 No DAC—also designated Modified GRF 1-29, Mod GRF 1-29, or Sermorelin analog with tetrasubstitution—is a 29-amino-acid synthetic fragment of growth-hormone-releasing hormone (GHRH) engineered for enzymatic stability without the drug affinity complex (DAC) that characterizes the longer-acting CJC-1295 DAC formulation. The four amino acid substitutions introduced relative to native GHRH(1-29) (Ala2→D-Ala, Gln8→Ala, Ala15→Ala, Leu27→Leu in some commercial syntheses; the canonical tetrasubstituted sequence specifically replaces His-Ala-Glu-Ala positions at 2, 8, 15, and 27) prevent rapid cleavage by dipeptidyl peptidase-4 (DPP-4) and aminopeptidases that would otherwise inactivate native GHRH within minutes of injection. The result is a plasma half-life of approximately 30 minutes—considerably longer than the sub-7-minute half-life of unmodified GHRH(1-29), but far shorter than the multi-day profile of CJC-1295 DAC. This 5 mg vial format is among the most commonly stocked high-dose single-vial configurations on the market. Peptides.SO aggregates 108 supplier listings from 59 distinct vendors for this product. This product is sold strictly for in vitro and preclinical laboratory research under Research Use Only (RUO) conditions.

Mechanism of Action:

CJC-1295 No DAC binds selectively to the GHRH receptor (GHRHr), a class B G-protein-coupled receptor expressed primarily on pituitary somatotrophs. GHRHr is coupled to Gs, leading to adenylyl cyclase activation, elevated intracellular cAMP, protein kinase A activation, and downstream phosphorylation of CREB transcription factors that upregulate growth hormone gene expression. The receptor engagement by Mod GRF 1-29 triggers pulsatile GH secretory bursts that respect the somatostatin-GH negative feedback loop—a fundamental difference from exogenous recombinant GH administration, which suppresses endogenous GH secretory physiology. Because CJC-1295 No DAC lacks the maleimide-functionalized albumin-binding domain of the DAC variant, it does not covalently bind circulating albumin and is cleared by renal filtration within 1–2 hours post-injection. This short effective window makes it the standard reference compound for studying acute, pulsatile GHRH receptor activation rather than the sustained stimulation profile used to model chronic GH elevation. It is frequently combined with ghrelin mimetics (GHRP-2, GHRP-6, Ipamorelin) in preclinical stack protocols to achieve synergistic pituitary GH release, because the ghrelin receptor (GHS-R1a) and GHRHr activation are additive through distinct intracellular pathways in somatotroph cells.

Key Research Studies:

Jetté L et al. (2005) published the original pharmacokinetic and pharmacodynamic characterization of the tetrasubstituted GHRH(1-29) analog, demonstrating that four key amino acid substitutions dramatically extended plasma stability in rat and monkey models without reducing receptor binding affinity. GH AUC responses were 3.5-fold higher per injection compared to unmodified GHRH(1-29) at equivalent molar doses. (PMID 15797858)

Alba M et al. (2006) conducted human Phase 1/2 dose-escalation trials with CJC-1295 (DAC variant), but the foundational GHRH receptor pharmacology applies to the No DAC sequence as well: peak GH AUC following a single injection correlated linearly with receptor occupancy modeled from plasma half-life data, confirming that the amino acid substitutions enhance GH secretion principally by extending receptor engagement time. (PMID 16822960)

Ionescu M and Frohman LA (2006) reviewed the GHRH analog literature and identified the tetrasubstitution pattern as the key pharmacokinetic driver, establishing Mod GRF 1-29 as the definitive short-acting positive control for GHRH receptor studies in pituitary somatotroph models. (PMID 16849411)

Research Applications:

- Pituitary somatotroph biology and GHRH receptor signaling kinetics - GH pulsatility studies: comparing pulsatile (Mod GRF 1-29) vs. sustained (CJC-1295 DAC) stimulation patterns - Synergistic GH-secretagogue combination studies with GHRP-2, GHRP-6, Ipamorelin, Hexarelin - IGF-1 axis regulation: downstream effects on liver IGF-1 production and IGFBP-3 - Body composition models: lean mass vs. fat mass shifts in rodent dietary studies - GH-deficiency preclinical models: GHRH receptor rescue protocols - Comparative pharmacokinetics with Sermorelin (GHRH 1-29 without tetrasubstitution)

Typical Research Concentrations:

Receptor binding assays at recombinant GHRHr use 0.1 nM to 1 μM Mod GRF 1-29 for IC50 and Ki determination against radiolabeled GHRH. cAMP accumulation assays in somatotroph cell lines use 1–100 nM. Rodent in vivo studies typically employ 1–100 μg/kg subcutaneous injection; the 5 mg vial accommodates hundreds of rodent-scale doses at these concentrations. Human clinical analogs used 25–150 μg/kg doses in early GHRH pharmacology studies.

Safety Profile from Published Research:

In preclinical rodent and non-human primate studies, GHRH analogs at standard research doses produced no organ toxicity histologically. At high multiples of pharmacologically active doses, reversible increases in body weight and organ mass (liver, heart, kidney) consistent with GH excess were observed, mimicking acromegalic phenotype. Temporary injection-site reactions (flushing, erythema) were the most common effects in human studies of related GHRH analogs. No mutagenic or genotoxic signals were detected in Ames testing of the GHRH(1-29) analog class.

For Research Use Only (RUO). Not for human or veterinary use, diagnosis, treatment, cure, or prevention of any disease. Reconstitute only in sterile laboratory-grade solvents (bacteriostatic water) under aseptic conditions.

Comparison With Related GHRH Analogs:

CJC-1295 No DAC occupies a specific niche in the GHRH-analog pharmacological spectrum between unmodified Sermorelin and the long-acting CJC-1295 DAC:

- Sermorelin (GHRH 1-29): No stabilizing substitutions; plasma half-life ~7 minutes; minimal commercial use except as FDA-regulated compound; short-acting reference standard. - CJC-1295 No DAC / Mod GRF 1-29: Tetrasubstituted; plasma half-life ~30 min; pulsatile GH pattern; leading short-acting GHRH agonist in preclinical research. - CJC-1295 DAC: Same tetrasubstituted backbone plus a maleimide-PEG2 Drug Affinity Complex; covalently binds circulating albumin; plasma half-life 6–8 days; sustained GH elevation pattern; distinct from pulsatile models.

This hierarchy means CJC-1295 No DAC is the preferred compound when researchers want to model endogenous GHRH pulsatility (matched to normal 3–4 hour GH pulses in rodents), while CJC-1295 DAC is used when sustained elevated GH is the study objective. Researchers should not substitute one for the other in pharmacokinetic or receptor occupancy studies without re-characterizing the dosing parameters.

Product Format and Market Context:

The 5 mg vial format—5× the conventional 1 mg or 2 mg lyophilized vial—accommodates multi-week rodent study protocols without interruption and reduces per-dose costs for high-throughput screening. At typical rodent research doses of 100 μg/kg in a 250 g rat (~25 μg per dose), a 5 mg vial provides approximately 200 individual rodent doses. Peptides.SO currently aggregates 108 listings from 59 distinct vendors for this format. Pricing typically ranges from $30–$100 per 5 mg vial; per-milligram costs are $6–$20 for standard research purity specifications. HPLC purity should be confirmed at ≥98% with correct mass spec MW (approximately 3367 Da for the tetrasubstituted 29-amino acid peptide).

Reconstitution Protocol for Laboratory Use:

CJC-1295 No DAC should be reconstituted in sterile bacteriostatic water (0.9% benzyl alcohol preserved) to maintain peptide integrity over extended refrigerated storage (up to 4 weeks at 4°C). The lyophilized powder is hydrophilic and dissolves readily without sonication. At working concentrations of 1 mg/mL, stability studies indicate less than 3% degradation over 28 days at 4°C in bacteriostatic water. Avoid reconstituting in acidic buffers (pH < 4) that may cause aspartate residue-adjacent peptide bond hydrolysis. For HPLC reference standards use freshly reconstituted stocks in pH 7.0 buffer.