CJC-1295 No-DAC 10mg

Introduction & Research Disclaimer

CJC-1295 No-DAC (also known as Mod GRF(1-29) or tetrasubstituted GRF(1-29)) is a synthetic 29-amino acid growth hormone-releasing hormone (GHRH) analogue engineered for enhanced proteolytic stability and extended bioactivity. It is a modified variant of endogenous GHRH(1-29)-NH₂ (sermorelin) incorporating four strategic amino acid substitutions that confer resistance to rapid enzymatic degradation. Biosim Peptides supplies CJC-1295 No-DAC (10 mg, lyophilized powder, ≥95% purity) exclusively for laboratory research applications. This product is not for human or veterinary use, not a drug, dietary supplement, or therapeutic agent. All research must comply with institutional, local, and national regulations. The purchaser certifies use solely within a qualified, institutionally approved research program.

Important distinction: CJC-1295 No-DAC is the peptide without the Drug Affinity Complex (DAC) moiety. The DAC-conjugated form (CJC-1295 with DAC) includes a maleimidopropionic acid linker that binds covalently to serum albumin, conferring a multi-day pharmacokinetic half-life. CJC-1295 No-DAC lacks this modification and exhibits a substantially shorter terminal half-life, making it the appropriate research tool for studies where pulse-like GHRH receptor activation is desired rather than sustained exposure.

Molecular Overview

CJC-1295 No-DAC is a linear, 29-residue peptide amide with a molecular weight of approximately 3,367 Da (freebase). The primary sequence is derived from the N-terminal bioactive fragment of human GHRH (residues 1–29), which retains full intrinsic activity at the GHRH receptor (GHRHR, a class B G protein-coupled receptor). Four amino acid substitutions distinguish CJC-1295 No-DAC from native GHRH(1-29):

• D-Tyr¹ replaces L-Tyr¹, conferring resistance to dipeptidyl peptidase-4 (DPP-4/CD26) cleavage, which otherwise inactivates native GHRH within minutes by cleaving the Tyr¹–Ala² bond.
• D-Ala² replaces L-Ala², further reinforcing DPP-4 resistance and extending N-terminal stability in plasma and tissue microenvironments.
• Gln⁸ replaces Asn⁸, eliminating a potential deamidation site and reducing non-enzymatic degradation pathways that compromise peptide integrity during storage and assay incubation.
• Arg²⁹-NH₂ (C-terminal amidation) replaces the native Arg²⁹–COOH, enhancing receptor binding affinity and protecting against carboxypeptidase-mediated C-terminal trimming.

These modifications collectively extend the functional half-life of the peptide from approximately 2–3 minutes (native GHRH(1-29)) to a reported 30–60 minutes in circulation, while preserving high-affinity binding and full agonist efficacy at the GHRH receptor (K_d in the low nanomolar range). The amidation of the C-terminus is critical: des-amidated analogues exhibit markedly reduced potency, typically by one to two orders of magnitude.

The peptide is unstructured in aqueous solution and is highly soluble in water and physiological buffers. Structural studies indicate that, like native GHRH, the bioactive conformation is an α-helical segment spanning residues ~6–20 when bound to the receptor, with the N-terminal tripeptide (D-Tyr¹–D-Ala²–Asp³) serving as the critical pharmacophore for receptor activation. The D-amino acid substitutions at positions 1 and 2 do not disrupt this bioactive conformation and, in fact, stabilize it by pre-organizing the N-terminal region into a receptor-competent state.

Mechanism of Action

CJC-1295 No-DAC activates the pituitary GHRH receptor (GHRHR), a member of the secretin/glucagon subfamily of class B GPCRs encoded by the GHRHR gene. The GHRHR is predominantly expressed on somatotroph cells of the anterior pituitary gland, where its activation triggers the Gα_s–adenylyl cyclase–cAMP–protein kinase A (PKA) signaling cascade.

Receptor Activation and Signal Transduction. Ligand binding to GHRHR induces a conformational change that promotes GDP–GTP exchange on Gα_s, liberating the Gα_s subunit to activate membrane-bound adenylyl cyclase. Elevated intracellular cAMP activates PKA, which phosphorylates the cAMP response element-binding protein (CREB) transcription factor. Phosphorylated CREB translocates to the nucleus and binds cAMP response elements (CREs) in the promoter region of the growth hormone (GH1) gene, driving GH mRNA transcription and subsequent GH protein synthesis, storage, and secretion. This pathway is pulsatile by nature: GHRH is released from hypothalamic arcuate nucleus neurons in episodic bursts, and somatotroph responsiveness is modulated by the reciprocal inhibitory hormone somatostatin.

GH Secretion Dynamics. Unlike sustained GHRH receptor activation — which rapidly desensitizes the receptor–adenylyl cyclase system and depletes the readily releasable GH pool — pulsatile stimulation preserves receptor responsiveness and maintains physiological GH secretory patterns. CJC-1295 No-DAC, by virtue of its short-to-intermediate half-life (relative to the DAC-conjugated form), more closely approximates the pulsatile GHRH stimulus when administered in discrete, intermittent research protocols. This is a critical experimental consideration: the DAC-conjugated form produces sustained, non-pulsatile GH elevations that may not recapitulate endogenous GH secretory dynamics.

IGF-1 Axis Coupling. GHRHR-mediated GH secretion stimulates hepatic (and local tissue) production of insulin-like growth factor-1 (IGF-1), which mediates many of the anabolic and growth-promoting effects attributed to GH. Circulating IGF-1 feeds back negatively to the hypothalamic–pituitary axis, suppressing further GHRH secretion and stimulating somatostatin release. Researchers studying the GHRH–GH–IGF-1 axis commonly employ CJC-1295 No-DAC as a pharmacological probe to dissect the relative contributions of pulsatile GHRH receptor activation to overall somatotrophic axis output.

Research Applications

CJC-1295 No-DAC is employed in several active areas of endocrinology and metabolism research:

• GH Pulsatility & Secretory Dynamics Research: Investigating the role of episodic versus continuous GHRH receptor stimulation on GH secretory patterns, receptor desensitization kinetics, and somatotroph releasable pool dynamics. CJC-1295 No-DAC’s intermediate half-life makes it a preferred tool over DAC-conjugated forms for experiments requiring intermittent receptor activation.
• GHRH Receptor Pharmacology: Elucidating ligand-binding determinants, receptor activation mechanisms, G protein coupling specificity (Gα_s vs. Gα_q/11 bias), and β-arrestin recruitment profiles for class B GPCRs, using CJC-1295 No-DAC as a stable, high-affinity agonist.
• Aging & Somatopause Models: With advancing age, spontaneous GH secretion declines (somatopause), attributable in part to reduced hypothalamic GHRH output and altered somatotroph responsiveness. CJC-1295 No-DAC is used in aging models to investigate whether exogenous pulsatile GHRH receptor stimulation can restore youthful GH secretory profiles and downstream IGF-1 production.
• Body Composition & Metabolism Studies: Research on the effects of GH/IGF-1 axis activation on lean body mass, adipose tissue distribution, lipid metabolism, and glucose homeostasis, using CJC-1295 No-DAC as a selective pharmacological activator of the GHRH receptor.
• Immune–Endocrine Interactions: GHRH, GH, and IGF-1 each exert immunomodulatory effects. CJC-1295 No-DAC is used to study how GHRH receptor activation influences lymphocyte subsets, cytokine profiles, and thymic function in aging and immune senescence models.
• Sleep & Circadian Rhythm Research: GH secretion is tightly coupled to slow-wave sleep. CJC-1295 No-DAC is employed in chronobiological studies to examine GHRH–sleep interactions and the temporal coupling between sleep architecture and somatotrophic axis activity.
• Comparative Pharmacology: Researchers directly compare CJC-1295 No-DAC with native GHRH(1-29), sermorelin acetate, CJC-1295 with DAC, tesamorelin, and other GHRH analogues to characterize pharmacokinetic–pharmacodynamic relationships and receptor activation kinetics.

Key Research Studies

The following peer-reviewed publications provide the scientific foundation for research involving CJC-1295 No-DAC and the broader GHRH analogue field:

Vance et al. (1985) established seminal evidence for a limited GHRH-releasable pool of GH, demonstrating that continuous 6-hour GHRH infusions in normal men produce an initial GH secretory burst followed by marked attenuation — the first clear demonstration of GHRH receptor desensitization and/or somatotroph GH depletion in humans. This work underpins the rationale for intermittent (rather than sustained) GHRH receptor agonism (J Clin Endocrinol Metab, PMID: 3917453).

Corpas et al. (1992) demonstrated that twice-daily subcutaneous administration of GHRH(1-29)-NH₂ (sermorelin) for two weeks partially reversed the age-related decline in GH and IGF-I in healthy older men. GH secretory pulse amplitude and IGF-I levels increased significantly, providing proof-of-concept that exogenous GHRH receptor activation can counteract somatopause-associated GH deficiency (J Clin Endocrinol Metab, PMID: 1379258).

Frohman & Kineman (1995) published a comprehensive review of GHRH synthesis, processing, receptor signaling, and the physiological regulation of pulsatile GH secretion. This review consolidated foundational knowledge of the GHRH–somatostatin interplay, GHRHR signaling cascades (cAMP/PKA/CREB), and the role of GHRH in somatotroph proliferation and differentiation (Recent Prog Horm Res, PMID: 7740158).

Khorram et al. (1997) provided evidence that [norleucine²⁷]GHRH(1-29)-NH₂ administration modulates immune function in aging humans. This study was among the first to demonstrate that GHRH analogue therapy influences lymphocyte subsets, natural killer cell activity, and cytokine production in older adults, broadening the scope of GHRH receptor biology beyond the somatotrophic axis (J Clin Endocrinol Metab, PMID: 9360511).

Giustina & Veldhuis (1998) published a landmark Endocrine Reviews article on the pathophysiology of neuroregulation of GH secretion, detailing the complex interplay of GHRH, somatostatin, ghrelin, and feedback signals (IGF-I, free fatty acids, glucocorticoids) that govern pulsatile GH output. This review is essential reading for researchers designing experiments with GHRH analogues (Endocr Rev, PMID: 9861545).

Veldhuis & Bowers (2003) reviewed the ensemble properties of human GH pulsatility, emphasizing that GH secretion is an emergent property of the GHRH–somatostatin–ghrelin triad rather than any single input. The review highlights how age, sex, body composition, and nutritional status modulate the GH axis, providing critical context for interpreting experimental results with GHRH analogues (J Endocrinol Invest, PMID: 14964431).

Teichman et al. (2006) reported the first clinical pharmacokinetic and pharmacodynamic data for CJC-1295 (the DAC-conjugated form) in healthy adults, demonstrating prolonged elevation of GH and IGF-I following a single subcutaneous injection. This study established the CJC-1295 molecular scaffold as a viable platform for GHRH analogue development and provided the comparative framework against which CJC-1295 No-DAC should be evaluated in research settings (J Clin Endocrinol Metab, PMID: 16352683).

Handling & Reconstitution Guidelines

CJC-1295 No-DAC is supplied as a sterile, lyophilized powder (10 mg per vial, ≥95% purity by HPLC). The following guidelines are recommended for research handling:

• Storage of Lyophilized Powder: Store at -20°C in a desiccated environment, protected from light and moisture. Lyophilized peptide is stable for the validated duration specified in the certificate of analysis when stored as directed.
• Reconstitution: CJC-1295 No-DAC is freely soluble in sterile water for injection, 0.9% sodium chloride (normal saline), or phosphate-buffered saline (PBS, pH 7.4). Recommended reconstitution concentrations are 0.5–5 mg/mL. Gently swirl or vortex to dissolve; the peptide typically enters solution within 30–60 seconds. Do not shake vigorously, as mechanical stress may promote aggregation of amphipathic helical regions.
• Aliquoting: For repeated use, aliquot reconstituted peptide into single-use volumes in sterile, low-protein-binding polypropylene or siliconized microcentrifuge tubes to minimize freeze-thaw degradation and adsorptive loss to tube walls. Store aliquots at -20°C or -80°C.
• pH & Buffer Compatibility: CJC-1295 No-DAC is stable in the pH range of 4.0–7.5. Avoid alkaline buffers (pH > 8.0), which accelerate deamidation at Gln⁸ and potential β-aspartyl shift reactions. For cell-based assays, confirm peptide stability in the chosen culture medium over the intended incubation period by HPLC or mass spectrometry.
• Freeze-Thaw Stability: Limit freeze-thaw cycles to no more than three in validated protocols. Each cycle may reduce bioactivity by 5–15%, depending on concentration and buffer composition. Lyophilized aliquots that have been reconstituted should not be re-lyophilized.
• Quantification: Peptide concentration can be verified by UV absorbance at 214 nm (peptide bond absorbance) or by quantitative amino acid analysis. CJC-1295 No-DAC contains a single tyrosine residue (D-Tyr¹) enabling absorbance at 280 nm (ε ~1,490 M⁻¹cm⁻¹), though the extinction coefficient is relatively low and 214 nm measurement or colorimetric assays (BCA, micro-BCA) may be preferred for dilute samples.

Safety & Precautionary Information

CJC-1295 No-DAC is a potent bioactive peptide and must be handled with appropriate laboratory precautions:

• General Laboratory Safety: Handle in a certified biosafety cabinet or chemical fume hood. Wear nitrile gloves, a laboratory coat, and protective eyewear. This product is for research use only and is not for human or animal administration outside of approved IACUC or equivalent institutional protocols.
• Inhalation/Aerosol Risk: Lyophilized peptide powder is lightweight; open vials carefully to avoid aerosolization. Use in a contained area and consider a dust mask if handling large quantities outside a hood.
• Skin & Eye Contact: Wash skin immediately with soap and water upon contact. For ocular exposure, rinse thoroughly with water for at least 15 minutes and seek medical evaluation.
• Biological Activity Awareness: CJC-1295 No-DAC activates the GHRH receptor with high potency (EC₅₀ in the low nanomolar range). Even low-level exposure could theoretically produce off-target effects in GHRHR-expressing tissues (including pituitary, some immune cells, and certain tumors). Handle accordingly.
• Disposal: Dispose of unused peptide and contaminated materials in accordance with institutional guidelines for bioactive peptides and chemical waste. Do not discard in general laboratory waste streams.
• Contraindicated Research Uses: This product is not validated for, and must not be used in, clinical diagnostic procedures, therapeutic development without appropriate regulatory authorization, or any application involving administration to food-producing animals.

Frequently Asked Questions

Q: What is the difference between CJC-1295 No-DAC and CJC-1295 with DAC?
A: CJC-1295 with DAC incorporates a maleimidopropionic acid Drug Affinity Complex that forms a covalent thioether bond with Cys³⁴ of serum albumin, extending its circulating half-life to approximately 5–8 days. CJC-1295 No-DAC lacks this moiety and consequently has a much shorter functional half-life (estimated 30–60 minutes). Researchers should select the No-DAC form when pulsatile or intermittent GHRH receptor stimulation is desired, and the DAC form when sustained receptor activation is the experimental objective.

Q: How does CJC-1295 No-DAC compare to sermorelin?
A: Both are 29-amino acid analogues of GHRH(1-29). Sermorelin (GHRH(1-29)-NH₂) is the unmodified sequence with C-terminal amidation. CJC-1295 No-DAC adds three additional substitutions: D-Tyr¹, D-Ala², and Gln⁸. These confer substantially greater resistance to DPP-4 and other peptidases, yielding a longer functional half-life and greater potency in research assays. Researchers often use both compounds in comparative pharmacology studies to assess the contribution of N-terminal D-amino acid substitutions to receptor activation kinetics and metabolic stability.

Q: What is the expected half-life of CJC-1295 No-DAC in research models?
A: The reported terminal elimination half-life in circulation is approximately 30–60 minutes for CJC-1295 No-DAC, compared to 2–3 minutes for native GHRH(1-29) and 5–8 days for CJC-1295 with DAC. However, researchers should note that half-life is model- and matrix-dependent; values in rodent models, cell culture media, and tissue homogenates may differ. It is recommended that researchers characterize peptide stability in their specific experimental system by HPLC or LC-MS/MS.

Q: Can CJC-1295 No-DAC be used in cell-based GHRH receptor signaling assays?
A: Yes. CJC-1295 No-DAC is a potent GHRHR agonist suitable for in vitro assays measuring cAMP accumulation, CREB phosphorylation, GH secretion (in primary somatotroph cultures or GH-secreting cell lines such as GH3 or GH4C1), and β-arrestin recruitment. Typical effective concentrations range from 0.1–100 nM depending on receptor expression level and assay endpoint. Always include native GHRH(1-29)-NH₂ and GHRH(1-44)-NH₂ as positive controls, and a GHRH receptor antagonist (e.g., [D-Arg², D-Phe⁶, D-Trp⁷·⁹, Leu¹¹]substance P or MZ-4-71) to confirm receptor specificity.

Q: Does CJC-1295 No-DAC cross-react with other receptors?
A: At concentrations used for GHRHR activation (≤100 nM), CJC-1295 No-DAC is highly selective for the GHRH receptor. At supraphysiological concentrations (>1 µM), cross-reactivity with related class B GPCRs (VIP receptors VPAC1/VPAC2, PAC1, secretin receptor) cannot be excluded. Researchers should include appropriate receptor specificity controls, particularly when working with tissues or cell lines that co-express multiple secretin-family receptors. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) may serve as comparative ligands for selectivity profiling.

References

1. Vance ML, Kaiser DL, Evans WS, et al. Evidence for a limited growth hormone (GH)-releasing hormone (GHRH)-releasable quantity of GH: effects of 6-hour infusions of GHRH on GH secretion in normal men. J Clin Endocrinol Metab. 1985;60(2):370-375. PMID: 3917453
2. Corpas E, Harman SM, Piñeyro MA, Roberson R, Blackman MR. Growth hormone (GH)-releasing hormone-(1-29) twice daily reverses the decreased GH and insulin-like growth factor-I levels in old men. J Clin Endocrinol Metab. 1992;75(2):530-535. PMID: 1379258
3. Frohman LA, Kineman RD. Growth hormone-releasing hormone: synthesis and signaling. Recent Prog Horm Res. 1995;50:187-216. PMID: 7740158
4. Khorram O, Yeung M, Vu L, Yen SS. Effects of [norleucine27]growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. J Clin Endocrinol Metab. 1997;82(11):3590-3596. PMID: 9360511
5. Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19(6):717-797. PMID: 9861545
6. Veldhuis JD, Bowers CY. Human GH pulsatility: an ensemble property regulated by age and gender. J Endocrinol Invest. 2003;26(9):799-813. PMID: 14964431
7. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone (GH) and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID: 16352683