CJC-1295 With DAC [Spray]

What is CJC-1295 With DAC Nasal Spray?

CJC-1295 with DAC is a synthetic 29-amino acid GHRH analogue developed by ConjuChem Biotechnologies in the early 2000s. It is based on the native GHRH(1–29) sequence, modified at positions 2, 8, 15, and 27 for metabolic stability. A maleimidopropionic acid Drug Affinity Complex (DAC) moiety is conjugated to C-terminal Lys30. This moiety covalently binds endogenous albumin, extending the circulating half-life to approximately 5.8 -- 8.1 days in preclinical and early-phase study models [Teichman et al., 2006; PMID 16352683]. CJC-1295 with DAC has not been approved as a registered pharmaceutical in any country.

The compound has been investigated in rodent and in vitro systems for GHRH receptor (GHRH-R) interactions on pituitary somatotroph cells. Research has examined GH/IGF-1 axis modulation and somatotroph proliferation. The nasal spray formulation is studied as a preclinical research delivery route. It is supported by evidence of olfactory bulb-mediated CNS transport for intranasally administered peptides in rodent models. Intranasal delivery also bypasses hepatic first-pass metabolism relative to systemic routes in preclinical pharmacokinetic models.

DISCLAIMER: This product is not a dietary supplement, is not approved by the Food and Drug Administration for human or veterinary use, and is not intended for human consumption or therapeutic self-administration.

Chemical Properties of CJC-1295 With DAC

How Does CJC-1295 With DAC Work?

CJC-1295 with DAC acts primarily at the GHRH receptor (GHRH-R), a Gs-coupled receptor expressed on pituitary somatotroph cells. Receptor binding activates adenylyl cyclase, increases intracellular cAMP, and stimulates both GH synthesis and pulsatile GH secretion. The DAC moiety extends residence time by forming a covalent bond with albumin. The following mechanistic observations are from preclinical and in vitro data only.

GHRH-R Binding and Somatotroph Activation

CJC-1295 with DAC binds the GHRH receptor on anterior pituitary somatotroph cells in preclinical preparations. Binding activates Gs-protein-coupled adenylyl cyclase signaling, elevating intracellular cAMP. This drives GH gene transcription and secretory granule release in somatotroph preparations. In GHRH-knockout mouse models, once-daily CJC-1295 administration restored pituitary GH mRNA and somatotroph cell mass to normal levels, as confirmed by immunohistochemistry [Alba et al., 2006; PMID 16822960].

Albumin-Mediated Half-Life Extension (DAC Mechanism)

The maleimidoproprionic acid DAC moiety on Lys(27) reacts selectively with the free thiol group of Cys-34 on endogenous albumin. This covalent albumin-binding confers a plasma half-life of approximately 5.8–8.1 days in early-phase investigational study data, versus minutes for native GHRH [Teichman et al., 2006; PMID 16352683]. The albumin bond allows sustained GHRH-R stimulation from a single administration in preclinical and investigational study models.

GH Pulsatility Preservation

In investigational study preparations, CJC-1295 with DAC increased basal (trough) GH levels approximately 7.5-fold while preserving GH pulse frequency and magnitude [Ionescu and Frohman, 2006; PMID 17018654]. The trough GH elevation, rather than altered pulse amplitude, was associated with elevated IGF-1 in these preparations. This pattern distinguishes CJC-1295 with DAC from short-acting GHRH analogs in experimental settings.

IGF-1 Axis and Downstream Protein Changes

Sustained GHRH-R activation by CJC-1295 with DAC was associated with changes in serum protein profiles in investigational study models. Apolipoprotein A1 and transthyretin isoforms were found to be downregulated; beta-hemoglobin and albumin C-terminal fragments were upregulated. IGF-1 levels showed a linear relationship with an albumin fragment-containing protein spot in 2D electrophoresis analyses [Sackmann-Sala et al., 2009; PMID 19386527]. These observations are from experimental systems only.

Intranasal Delivery & Pharmacokinetics

Olfactory Bulb-Mediated CNS Transport

When administered intranasally in preclinical rodent model systems, peptide compounds can access the central nervous system through the olfactory nerve (cranial nerve I) pathway. Compounds deposited on the olfactory mucosa are transported along olfactory axons through the cribriform plate to the olfactory bulb, from which access to deeper CNS structures has been characterized in rodent preparations. The olfactory and trigeminal nerve pathways for nose-to-brain peptide transport have been investigated in preclinical studies of peptide and protein delivery [Wong et al., 2024; PMID 38441832]. No compound-specific olfactory transport data for CJC-1295 with DAC has been published.

Hepatic First-Pass Metabolism Bypass

The intranasal route avoids portal circulation and hepatic first-pass metabolic processing. For peptide research compounds subject to rapid proteolytic degradation in the gastrointestinal environment, intranasal delivery has been investigated as a route that may preserve compound integrity relative to oral administration in preclinical pharmacokinetic models. CJC-1295 with DAC is a large peptide susceptible to GI and hepatic peptidase activity; intranasal delivery bypasses this environment. These observations are derived from preclinical studies and do not constitute evidence of efficacy via any route in human subjects.

Nasal Mucosal Absorption

CJC-1295 with DAC has a molar mass of 3647.25 g/mol (approximately 3.65 kDa). This molecular weight falls in the upper range of the 1–5 kDa bracket, indicating paracellular and endocytic uptake mechanisms are the likely predominant absorption pathways at the nasal mucosa. At this size, transcellular lipid-bilayer diffusion is not expected to be a significant route. Olfactory nerve transport may contribute to CNS access at this molecular weight in preclinical preparations. The DAC-albumin bond adds further molecular weight upon binding (~67 kDa for albumin), which is relevant to post-absorption distribution modeling.

Compound-Specific Pharmacokinetics

Specific intranasal pharmacokinetic data for CJC-1295 with DAC in standardized preclinical models is not available in the published literature as of June 2026. Published pharmacokinetic data, including the 5.8–8.1 day half-life, are derived exclusively from subcutaneous administration studies [Teichman et al., 2006; PMID 16352683]. The olfactory bulb transport pathway has been characterized for structurally related peptide compounds in rodent model systems. Researchers should account for the absence of compound-specific intranasal pharmacokinetic data when designing laboratory protocols.

Key Research Findings

• GH/IGF-1 Elevation (Investigational Study Model): Single subcutaneous CJC-1295 with DAC administration produced dose-dependent 2–10-fold GH increases lasting ≥6 days and 1.5–3-fold IGF-1 increases lasting 9–11 days in healthy adult subject preparations [Teichman et al., 2006; PMID 16352683]
• GH Pulsatility Preserved (Investigational Study Model): CJC-1295 with DAC increased mean and trough GH levels with preserved pulse frequency and amplitude; trough GH was elevated ~7.5-fold relative to baseline in adult male preparations [Ionescu and Frohman, 2006; PMID 17018654]
• Growth Normalization (GHRH-KO Mouse Model): Once-daily CJC-1295 administration normalized body weight, bone length, and pituitary somatotroph cell mass in GHRH-knockout mice over 5 weeks; less frequent dosing produced partial normalization only [Alba et al., 2006; PMID 16822960]
• Serum Protein Biomarker Changes (Investigational Study Model): CJC-1295 with DAC was associated with downregulation of apolipoprotein A1 and transthyretin isoforms and upregulation of beta-hemoglobin and albumin fragments; IGF-1 correlated linearly with specific protein spot intensities [Sackmann-Sala et al., 2009; PMID 19386527]

Findings in rows 1 and 2 are derived from early-phase investigational human studies. Findings in rows 3 and 4 are from preclinical rodent and in vitro systems. None of these observations constitutes evidence of efficacy or safety for CJC-1295 with DAC nasal spray.

What are the Potential Research Applications?

In controlled laboratory environments, CJC-1295 with DAC nasal spray has been investigated for the following research applications. These are observed in preclinical and in vitro contexts only and do not constitute claims of efficacy or safety in any organism.

GH/IGF-1 Axis Modulation Research

CJC-1295 with DAC has been investigated as a tool compound for modulating GH and IGF-1 secretory dynamics in pituitary somatotroph preparations. Research applications include dose-response characterization of GHRH-R-mediated cAMP elevation and examination of downstream GH mRNA and protein output in anterior pituitary cell culture systems.

Somatotroph Biology and Proliferation

In GHRH-knockout rodent models, CJC-1295 has been used to examine the relationship between sustained GHRH-R stimulation and somatotroph cell proliferation. These applications include immunohistochemical characterization of pituitary GH-positive cell populations and Northern blot quantification of GH mRNA after sustained compound exposure.

Albumin-Binding Pharmacokinetic Modeling

The DAC moiety provides a research model for studying covalent albumin-binding pharmacokinetics. CJC-1295 with DAC is investigated in preclinical settings as a reference compound for sustained-release peptide delivery strategies, including half-life extension via endogenous protein conjugation.

Serum Proteomics Research

CJC-1295 with DAC has been used in preclinical and investigational study settings to examine GH- and IGF-1-associated serum protein profile changes by 2D gel electrophoresis and mass spectrometry. These applications are relevant to biomarker research for GH axis activity in experimental preparations.

What are the Potential Side Effects?

Researchers in preclinical and in vitro settings have noted the following observations. Long-term safety and toxicity profiles remain incompletely characterized, and no human safety data has been established.

• Injection site reactions (preclinical): Subcutaneous administration in animal models was associated with local injection site inflammation and necrosis in nonclinical studies reviewed in FDA advisory committee documents (December 2024); relevance to intranasal administration is not characterized
• Hematological observations (nonclinical): Reduced hemoglobin levels were noted in nonclinical studies; the mechanism and reproducibility across preclinical preparations have not been fully characterized in published literature
• Lipid parameter changes (nonclinical): Elevated cholesterol was observed in nonclinical toxicology studies; the relationship to GHRH-R-mediated signaling versus formulation-related effects has not been established
• Reduced food and water intake (nonclinical): Decreased food and water intake was reported in nonclinical studies; this observation has not been characterized in intranasal delivery contexts
• Pituitary cell DNA changes (nonclinical): DNA damage in pituitary cells was noted in nonclinical studies referenced in regulatory documents; the dose and exposure conditions associated with this observation are not fully published
• Absence of intranasal-specific safety data: No safety or tolerability data specific to the intranasal route of administration for CJC-1295 with DAC has been published in the peer-reviewed literature as of June 2026

No human safety or tolerability data have been established for CJC-1295 with DAC nasal spray. These observations are derived from experimental systems and should not be extrapolated to human or animal outcomes.

Risk & Handling

Handling Precautions

Standard laboratory PPE is required: nitrile gloves, a laboratory coat, and eye protection. The following nasal spray-specific precautions apply:

1. Do not direct the nasal spray actuator toward the face, eyes, or mucous membranes during handling, testing, or transfer. CNS-active compounds may produce pharmacological effects via inadvertent intranasal self-exposure.

2. Handle the nasal spray solution in a clean laboratory environment. For aliquoting or analytical sampling, use a laminar flow cabinet.

3. The nasal spray solution is an aqueous formulation susceptible to microbial contamination if compromised. Handle under aseptic conditions. Discard if the solution appears cloudy, discolored, or shows particulate matter.

4. Avoid aerosol generation during any manipulation of the nasal spray solution.

Exposure Risks

Risk Tier: MODERATE

CJC-1295 with DAC acts on the GH/IGF-1 axis via pituitary GHRH receptor engagement. Nonclinical studies have identified pituitary cell DNA changes and hematological observations at exposure levels used in animal studies. No acute toxicity data specific to intranasal exposure is available. Inadvertent intranasal self-exposure during laboratory handling carries a risk of uncharacterized systemic absorption and GH-axis modulation. No human safety or tolerability data have been established for CJC-1295 with DAC nasal spray. Researchers should handle this compound with precautions appropriate to a biologically active peptide with a characterized pituitary mechanism of action.

Storage

• In-use nasal spray: Store at 2–8°C. Use within 28 days of first actuation. Protect from light. Keep upright.
• DO NOT FREEZE the ready-to-use nasal spray formulation. Freezing alters pH, buffer stability, excipient integrity, and spray actuation properties.
• Lyophilized bulk stock (if applicable): Store at −20°C in sealed, desiccated, light-protected containers. Avoid repeated freeze-thaw cycles.
• Discard any solution that appears cloudy, discolored, or shows visible particulate matter.

FAQs

Q: How does intranasal administration facilitate CNS access for CJC-1295 with DAC in preclinical research models?

A: Intranasal application allows peptide compounds to access the CNS via the olfactory nerve (cranial nerve I) and trigeminal nerve pathways. Compounds deposited on the olfactory mucosa are transported along olfactory axons through the cribriform plate to the olfactory bulb, bypassing the blood-brain barrier. This transport pathway has been characterized for peptide compounds of comparable molecular weight ranges in rodent models [Wong et al., 2024; PMID 38441832], though no compound-specific olfactory transport data exists for CJC-1295 with DAC. No compound-specific olfactory transport data exists for CJC-1295 with DAC. Intranasal delivery also avoids hepatic first-pass metabolism. No human CNS delivery data have been established for research-grade CJC-1295 with DAC nasal spray.

Q: What is the recommended storage and in-use shelf life for CJC-1295 with DAC nasal spray?

A: Sealed product should be stored at 2–8°C, protected from light. Once first actuated, in-use shelf life is 28 days at 2–8°C. DO NOT FREEZE the ready-to-use solution - freezing destabilizes the buffer, alters pH, and may damage spray actuation. Lyophilized bulk stock should be stored at −20°C in sealed, desiccated, light-protected conditions. Discard if the solution shows cloudiness, discoloration, or particulate matter.

Q: Is the CJC-1295 with DAC nasal spray formulation suitable for cell culture or in vitro assay systems?

A: The formulation is prepared in isotonic saline (0.9% NaCl, pH 5.5–6.5) without preservatives. The preservative-free composition reduces cytotoxicity risk in sensitive cell preparations relative to preserved formulations. However, researchers should validate the vehicle independently in their specific cell system. The formulation pH (5.5–6.5) is below the typical cell culture pH range (7.2–7.4); dilution into culture medium before application is recommended. Researchers are responsible for confirming compatibility with their assay system.

Q: What is the half-life of CJC-1295 with DAC in preclinical models?

A: The plasma half-life of CJC-1295 with DAC - derived from subcutaneous administration in investigational study models - is approximately 5.8–8.1 days [Teichman et al., 2006; PMID 16352683]. This extended half-life is a direct consequence of the DAC-mediated covalent bond with endogenous albumin at Cys-34. No pharmacokinetic data specific to the intranasal route have been published as of June 2026.

Q: How does CJC-1295 with DAC differ from CJC-1295 without DAC?

A: CJC-1295 without DAC (also called Modified GRF(1-29)) lacks the maleimidoproprionic acid moiety on Lys(27). It does not form a covalent albumin bond and has a significantly shorter half-life of minutes to hours in preclinical preparations. CJC-1295 with DAC is the albumin-binding form with a multi-day half-life. The two compounds differ in molecular weight (3647.25 vs 3367.9 g/mol), half-life profile, and dosing interval in preclinical research protocols.

Q: What toxicity observations have been reported in preclinical or nonclinical studies?

A: Nonclinical studies referenced in FDA advisory committee documents (December 2024) reported findings of reduced food and water intake, softer stools, decreased activity, vomiting, reduced hemoglobin, elevated cholesterol, injection site inflammation and necrosis, and DNA damage in pituitary cells. These observations were from nonclinical animal studies at exposure levels that may not correspond to research-use concentrations. No human safety or tolerability data have been established for CJC-1295 with DAC nasal spray. Visit RCD Bio to explore our full research compound catalog.