Mod GRF 1-29 (CJC-1295 No Dac) [Nasal Spray]

Description

What is Mod GRF 1-29 (CJC-1295 No DAC) Nasal Spray?

Mod GRF 1-29 (also known as CJC-1295 without DAC, or tetrasubstituted GRF(1-29)) is a synthetic 29-amino acid analog of growth hormone-releasing hormone (GHRH). It is structurally based on sermorelin (GRF 1-29), the shortest fully functional fragment of native GHRH, with four amino acid substitutions at positions 2, 8, 15, and 27. These substitutions were introduced to improve metabolic stability and resistance to enzymatic degradation. The substitution at position 2 replaces L-alanine with D-alanine (D-Ala²), conferring resistance to rapid cleavage by dipeptidyl peptidase-IV (DPP-IV). Positions 8 (Asn to Gln), 15 (Gly to Ala), and 27 (Met to Leu) provide further protease resistance. Mod GRF 1-29 lacks the Drug Affinity Complex (DAC) maleimidoproprionic acid moiety present on CJC-1295 with DAC, meaning it does not covalently bind endogenous albumin and has a substantially shorter plasma half-life. Mod GRF 1-29 has not been approved as a registered pharmaceutical in any country.

The compound has been investigated in rat anterior pituitary cell preparations and in vitro systems for its interactions with the GHRH receptor (GHRH-R), cAMP-mediated GH secretion, and DPP-IV stability relative to the parent sermorelin sequence. Research using tetrasubstituted hGRF(1-29) forms has confirmed GH-releasing activity in cultured rat anterior pituitary cells from picomolar to micromolar concentrations and elevated GH in rat plasma following subcutaneous administration [Jetté et al., 2005; PMID 15817669]. The nasal spray formulation is studied as a preclinical research delivery route. Evidence of olfactory bulb-mediated CNS transport for intranasally administered peptides in rodent models supports this approach. Intranasal delivery also bypasses hepatic first-pass metabolism relative to systemic routes in preclinical pharmacokinetic models.

Mod GRF 1-29 Nasal Spray, as supplied by RCDbio, 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. All RCDbio research compounds are supplied strictly for laboratory and research purposes only.

DISCLAIMER: Mod GRF 1-29 (CJC-1295 No DAC) Nasal Spray has not been approved by the Food and Drug Administration for human use, consumption, or any therapeutic application. This product is supplied exclusively for in vitro and preclinical laboratory research purposes.

Chemical Properties of Mod GRF 1-29 (CJC-1295 No DAC)

How Does Mod GRF 1-29 Work?

Mod GRF 1-29 acts at the GHRH receptor (GHRH-R), a Gs-protein-coupled receptor expressed on anterior pituitary somatotroph cells. Receptor binding activates adenylyl cyclase, elevates intracellular cAMP, and stimulates GH gene transcription and pulsatile GH secretion. The four amino acid substitutions improve DPP-IV resistance and metabolic stability without altering the GHRH-R binding pharmacophore. The following mechanistic observations are from preclinical and in vitro data only.

GHRH-R Binding and DPP-IV Resistance

Mod GRF 1-29 binds the GHRH-R at the anterior pituitary. The D-Ala² substitution prevents cleavage of the His¹-D-Ala² peptide bond by DPP-IV, the primary enzyme responsible for rapid inactivation of native GHRH and sermorelin in plasma. DPP-IV cleavage of the Tyr¹-Ala² bond in sermorelin generates the biologically inactive fragment GRF(3-29), which does not bind GHRH-R. By substituting L-Ala² with D-Ala², Mod GRF 1-29 retains GHRH-R binding while resisting this inactivating cleavage in preclinical preparations [Jetté et al., 2005; PMID 15817669]. In vitro stability against DPP-IV was confirmed in albumin bioconjugate studies of tetrasubstituted hGRF(1-29) forms.

Adenylyl Cyclase Activation and GH Secretion

GHRH-R engagement by Mod GRF 1-29 activates Gs-protein-coupled adenylyl cyclase, increasing intracellular cAMP in anterior pituitary somatotroph cells. This drives GH gene transcription and secretory granule release. In cultured rat anterior pituitary cells, tetrasubstituted hGRF(1-29) increased GH secretion from picomolar to micromolar concentrations in a dose-dependent manner [Jetté et al., 2005; PMID 15817669]. In Sprague-Dawley rat models, subcutaneous administration produced acute GH elevation in plasma. These observations are from preclinical rodent and in vitro preparations only.

GH Pulsatility and IGF-1 Axis

GHRH-R agonists acting via the cAMP pathway preserve pulsatile GH secretion dynamics in preclinical and investigational study model systems. In an investigational study, preparations using CJC-1295 with DAC (the albumin-binding form of the same tetrasubstituted scaffold), preserved GH pulse frequency and magnitude, which were maintained alongside elevated trough GH levels [Ionescu and Frohman, 2006; PMID 17018654]. Mod GRF 1-29 lacks the albumin-binding DAC moiety, producing a shorter-duration GH pulse profile consistent with its estimated plasma half-life of approximately 30 minutes in preclinical preparations.

GHRH-KO Mouse Growth Normalization

In GHRH-knockout (GHRHKO) mouse models, CJC-1295 (the tetrasubstituted hGRF(1-29) scaffold with DAC) administered once daily normalized body weight, bone length, somatotroph cell mass, and GH mRNA levels over 5 weeks [Alba et al., 2006; PMID 16822960]. These findings in GHRHKO preparations demonstrate that GHRH-R engagement by tetrasubstituted GRF(1-29) analogs is sufficient to restore somatotroph function in GH-deficient rodent model systems. This context is applicable to the Mod GRF 1-29 scaffold as the same tetrasubstituted amino acid sequence.

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 Mod GRF 1-29 have been published.

Hepatic First-Pass Metabolism Bypass

The intranasal route avoids portal circulation and hepatic first-pass metabolic processing. Mod GRF 1-29, as a 29-amino acid peptide, is susceptible to peptidase activity in the GI environment. The D-Ala² substitution provides resistance to DPP-IV at the nasal mucosa and in systemic circulation, which is directly relevant to the intranasal delivery context. DPP-IV is expressed in nasal epithelial tissue. These observations are derived from preclinical studies and do not constitute evidence of efficacy via any route in human subjects.

Nasal Mucosal Absorption

Mod GRF 1-29 has a molar mass of 3367.9 g/mol (approximately 3.37 kDa). This molecular weight falls within 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. The D-Ala² substitution also provides partial resistance to nasal mucosal DPP-IV, which is relevant to formulation stability during nasal residence time. Specific nasal mucosal permeability coefficients for Mod GRF 1-29 have not been published.

Compound-Specific Pharmacokinetics

Specific intranasal pharmacokinetic data for Mod GRF 1-29 in standardized preclinical models is not available in the published literature as of June 2026. The estimated plasma half-life of Mod GRF 1-29 following subcutaneous administration is approximately 30 minutes, substantially longer than sermorelin (~10-12 min) due to DPP-IV resistance, but substantially shorter than CJC-1295 with DAC (5.8-8.1 days). These values are derived from non-intranasal administration data and cannot be directly transferred to the intranasal route. Researchers should account for the absence of intranasal-specific pharmacokinetic parameters when designing laboratory protocols.

Key Research Findings

DPP-IV Resistance and GH Secretion in Rat Anterior Pituitary (Tetrasubstituted hGRF(1-29)): Albumin-conjugated tetrasubstituted hGRF(1-29) showed enhanced DPP-IV stability in vitro and stimulated GH secretion in cultured rat anterior pituitary cells; the best compound (CJC-1295) showed a 4-fold increase in GH area under the curve versus native hGRF(1-29) in Sprague-Dawley rat plasma following subcutaneous administration [Jetté et al., 2005; PMID 15817669]

GH Pulsatility Preservation with Sustained GHRH-R Stimulation (Investigational Study Model): Extended GHRH-R stimulation via the tetrasubstituted GRF(1-29)-albumin scaffold (CJC-1295 with DAC) preserved GH pulse frequency and amplitude while elevating trough GH levels approximately 7.5-fold; this confirmed that the tetrasubstituted GHRH-R agonist scaffold maintains pulsatile GH dynamics [Ionescu and Frohman, 2006; PMID 17018654]

Growth Normalization in GHRH-KO Mouse Model: Once-daily tetrasubstituted GRF(1-29)-albumin analog (CJC-1295 with DAC) normalized body weight, bone length, and somatotroph cell mass in GHRHKO mice over 5 weeks; less frequent dosing produced only partial normalization, demonstrating receptor-mediated somatotroph restoration via the tetrasubstituted GRF(1-29) scaffold [Alba et al., 2006; PMID 16822960]

All findings listed above are derived from preclinical in vitro and in vivo model systems using rat, mouse, and human albumin preparations. References to CJC-1295 with DAC in rows 2 and 3 describe data obtained using the same tetrasubstituted hGRF(1-29) scaffold and are cited for mechanistic context only. These observations do not constitute evidence of efficacy or safety for Mod GRF 1-29 nasal spray in any organism. No human clinical data has been established for research-grade Mod GRF 1-29 administered via the intranasal route.

What are the Potential Research Applications?

In controlled laboratory environments, Mod GRF 1-29 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.

GHRH-R Binding and DPP-IV Stability Research

Mod GRF 1-29 is investigated as a proteolytically stable GHRH-R agonist reference compound in studies comparing DPP-IV resistance among GHRH analogs. Research applications include in vitro DPP-IV stability assays comparing Mod GRF 1-29, sermorelin, and other GRF fragments, and characterization of GHRH-R/cAMP signaling in anterior pituitary somatotroph cell preparations.

Short-Acting GHRH-R Agonist Pharmacokinetic Modeling

Mod GRF 1-29’s half-life (~30 min) occupies a position between sermorelin (~10-12 min) and CJC-1295 with DAC (5.8-8.1 days), making it a useful intermediate reference compound for comparative pharmacokinetic modeling of GHRH-R agonist half-life extension strategies in preclinical peptide delivery research.

GH Pulse Profile Research

In preclinical rodent preparations, Mod GRF 1-29 is used to study pulsatile GH secretion dynamics in the context of short-duration GHRH-R engagement. Research applications include GH pulse profile characterization following single or repeated administration, comparison with longer-acting GHRH-R agonists, and somatostatin feedback regulation studies in rodent model systems.

Intranasal GHRH-R Delivery Research

Mod GRF 1-29 is investigated as a preclinical tool for studying intranasal delivery of metabolically stabilized GHRH fragment peptides. Research applications include nasal mucosal DPP-IV stability studies, comparison of intranasal GH-axis engagement between Mod GRF 1-29 and sermorelin, and olfactory transport pathway characterization for 3.3-3.4 kDa peptides in rodent model systems.

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 have been established for the research-grade nasal spray formulation.

• GH axis dysregulation (preclinical class data): Continuous or repeated GHRH-R stimulation in preclinical models has been associated with somatostatin feedback upregulation and potential GH secretory desensitization; these observations are from class-level GHRH analog data and have not been characterized specifically for the intranasal route of Mod GRF 1-29
• Cortisol and ACTH co-stimulation (preclinical class context): GHRH analogs at higher doses have been associated with transient ACTH/cortisol responses in some preclinical preparations; this observation is more prominent with GHRH-independent secretagogues (e.g., GHRP-6) than with GHRH-R agonists but has not been formally excluded for Mod GRF 1-29 in preclinical studies
• Injection site reactions (class context): Mild injection site reactions have been reported in investigational study models with related GHRH analogs; relevance to the intranasal route has not been characterized for Mod GRF 1-29
• Absence of intranasal-specific safety data: No safety or tolerability data specific to the intranasal route of administration for Mod GRF 1-29 has been published in the peer-reviewed literature as of June 2026

No human safety or tolerability data have been established for Mod GRF 1-29 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: LOW-MODERATE

Mod GRF 1-29 acts via GHRH-R-mediated GH/IGF-1 axis modulation. The compound’s pituitary mechanism of action means inadvertent intranasal self-exposure carries a risk of transient GH axis modulation. No acute toxicity events have been reported in published preclinical literature at research-use dose ranges. No human safety or tolerability data has been established for Mod GRF 1-29 nasal spray. Researchers should handle this compound with precautions appropriate to a biologically active pituitary-targeting peptide.

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 Mod GRF 1-29 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 structurally related GHRH fragment peptides in rodent models [Wong et al., 2024; PMID 38441832]. No compound-specific olfactory transport data exists for Mod GRF 1-29. The D-Ala2 substitution also confers resistance to DPP-IV, which is expressed in nasal epithelium, potentially improving intranasal stability relative to sermorelin. No human CNS delivery data has been established for research-grade Mod GRF 1-29 nasal spray.

Q: What is the recommended storage and in-use shelf life for Mod GRF 1-29 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 Mod GRF 1-29 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. Researchers should validate the vehicle independently in their specific cell system. The formulation pH (5.5-6.5) is below the typical cell culture 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 plasma half-life of Mod GRF 1-29 in preclinical models?

A: The plasma half-life of Mod GRF 1-29 following subcutaneous administration is estimated at approximately 30 minutes, based on DPP-IV resistance conferred by the D-Ala2 substitution. This is substantially longer than sermorelin (~10-12 min) but substantially shorter than CJC-1295 with DAC (5.8-8.1 days). No formal pharmacokinetic parameters specific to the intranasal route have been published as of June 2026.

Q: How does Mod GRF 1-29 differ from sermorelin and CJC-1295 with DAC?

A: All three are GHRH(1-29)-based GHRH-R agonists. Sermorelin is the native, unmodified GRF(1-29) sequence with a half-life of approximately 10-12 minutes and is susceptible to DPP-IV cleavage at the Tyr1-Ala2 bond. Mod GRF 1-29 carries four amino acid substitutions (D-Ala2, Gln8, Ala15, Leu27) for DPP-IV resistance and metabolic stability, extending the half-life to approximately 30 minutes. CJC-1295 with DAC adds a DAC albumin-binding moiety to the Mod GRF 1-29 scaffold, extending the half-life to 5.8-8.1 days. All three act via the GHRH-R/cAMP pathway in somatotroph preparations.

Q: What is the WADA status of Mod GRF 1-29?

A: Mod GRF 1-29 is prohibited under the 2026 WADA Prohibited List, Category S2.2.4 (Growth Hormone Releasing Factors), as a synthetic GHRH analogue , as a synthetic GHRH analog. This prohibition applies both in and out of competition for all WADA Code signatories. RCDbio products are supplied for laboratory research purposes only and are not supplied for use in competitive sport contexts.

Q: What toxicity observations have been reported for Mod GRF 1-29?

A: No formal acute or subchronic toxicology studies for Mod GRF 1-29 are available in the peer-reviewed literature. The compound class (GHRH analogs) has been associated with mild injection site reactions and transient GH/IGF-1 axis changes in investigational study models. Intranasal-specific toxicology data is not available. No human safety or tolerability data has been established for Mod GRF 1-29 nasal spray.

Related Research Compounds

Researchers investigating Mod GRF 1-29 nasal spray may also be interested in the following compounds currently available for laboratory research at RCDbio:

Sermorelin Nasal Spray — The unmodified native GRF(1-29) GHRH-R agonist investigated in preclinical somatotroph preparations for short-duration GHRH-R stimulation and comparative stability studies with Mod GRF 1-29.

CJC-1295 With DAC Nasal Spray — The albumin-binding tetrasubstituted GRF(1-29) analog investigated for sustained GH/IGF-1 axis modulation in preclinical somatotroph and GHRH-KO mouse model systems.

Ipamorelin Nasal Spray — A selective GHS-R1a agonist pentapeptide investigated in preclinical models for GH secretagogue activity via a pathway distinct from GHRH-R signaling; used in combination research with GHRH-R agonists in preclinical preparations.

All products listed are for laboratory and research purposes only.

References

1. Jetté, L., Léger, R., Thibaudeau, K., Benquet, C., Robitaille, M., Pellerin, I., Paradis, V., van Wyk, P., Pham, K., & Bridon, D.P. (2005). Human growth hormone-releasing factor (hGRF)1-29-albumin bioconjugates activate the GRF receptor on the anterior pituitary in rats: identification of CJC-1295 as a long-lasting GRF analog. Endocrinology, 146(7), 3052-3058.

   https://pubmed.ncbi.nlm.nih.gov/15817669/

2. Ionescu, M., & Frohman, L.A. (2006). Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology and Metabolism, 91(12), 4792-4797.

   https://pubmed.ncbi.nlm.nih.gov/17018654/

3. Alba, M., Fintini, D., Sagazio, A., Lawrence, B., Castaigne, J.P., Frohman, L.A., & Salvatori, R. (2006). Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American Journal of Physiology — Endocrinology and Metabolism, 291(6), E1290-E1294.

   https://pubmed.ncbi.nlm.nih.gov/16822960/

4. Wong, C.Y.J., Baldelli, A., Hoyos, C.M., et al. (2024). Insulin delivery to the brain via the nasal route: unraveling the potential for Alzheimer’s Disease therapy. Drug Delivery and Translational Research, 14(7), 1776-1793.

   https://pubmed.ncbi.nlm.nih.gov/38441832/

Research Transparency Note: No peer-reviewed publications specific to intranasal delivery of Mod GRF 1-29 are available as of June 2026. References 2 and 3 above describe studies using CJC-1295 with DAC, which shares the same tetrasubstituted hGRF(1-29) scaffold as Mod GRF 1-29 and are cited for mechanistic context only. The olfactory transport pathway evidence in Reference 4 is class-level and applies to structurally related peptide hormones in rodent models.

Disclaimer

Mod GRF 1-29 (CJC-1295 No DAC) Nasal Spray is exclusively for laboratory research purposes. RCDbio products are not intended to diagnose, prevent, treat, or cure any disease or medical condition.

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