CJC-1295 No DAC (Mod GRF 1-29) Peptide 10mg – Tetrasubstituted GHRH Analog

KEY SPECIFICATIONS:

PRODUCT OVERVIEW:

CJC-1295 No DAC, also known as Modified GRF 1-29, is a tetrasubstituted synthetic analog of natural Growth Hormone-Releasing Hormone (GHRH 1-29). Specifically, this peptide improves stability against enzymatic degradation while maintaining natural pulsatile release characteristics. Unlike the DAC (Drug Affinity Complex) version, this peptide lacks albumin-binding conjugation. Consequently, it exhibits a shorter half-life that more closely mimics physiological GHRH dynamics.

Research demonstrates that the D-Alanine at position 2 creates significant resistance to dipeptidyl peptidase-4 (DPP-4). Furthermore, this modification extends bioavailability while preserving receptor binding affinity. Therefore, the absence of DAC modification makes this variant particularly suitable for studies requiring precise control of pulsatile hormone dynamics. BIONIX supplies CJC-1295 No DAC with ≥99% HPLC-verified purity.

MECHANISM OF ACTION:

CJC-1295 No DAC acts as an agonist at the GHRH receptor, initiating a well-characterized signaling cascade.

Structural Modifications

The peptide incorporates four strategic amino acid substitutions compared to native GHRH (1-29):

D-Alanine at Position 2: This modification is critical for research applications. Native GHRH is rapidly cleaved between positions 2 and 3 by DPP-4, resulting in a plasma half-life of only ~7 minutes. Consequently, the D-amino acid configuration creates a stereochemical barrier preventing DPP-4 recognition. As a result, bioavailability extends to ~30 minutes.

Additional Stabilizing Modifications: The remaining substitutions address other degradation pathways including deamidation (Asn→Gln), backbone flexibility (Gly→Ala), and methionine oxidation (Met→Leu/Nle). Therefore, the tetrasubstituted structure provides comprehensive metabolic stability.

GHRH Receptor Signaling

The GHRH-R is a Class B G-protein-coupled receptor expressed on anterior pituitary somatotrophs:

Additionally, GHRH-R activation involves voltage-gated calcium channels. Consequently, calcium influx triggers vesicle fusion and rapid GH exocytosis. Moreover, this dual signaling enables acute secretory responses in research models.

No DAC vs DAC Comparison

Crucially, the absence of DAC modification determines release characteristics:

Pulsatile Significance: No DAC signaling more closely mimics natural hypothalamic release patterns. Consequently, this may be important for maintaining normal receptor sensitivity and feedback regulation in research models.

Comparison to Native GHRH

RESEARCH APPLICATIONS:

GHRH Receptor Binding Studies

CJC-1295 No DAC enables investigation of ligand-receptor interactions. Specifically:

• Assay Types: Radioligand binding (Kd, Bmax), competition binding (IC50, Ki), surface plasmon resonance (kon, koff), fluorescence polarization
• Research Questions: How do tetrasubstituted modifications affect binding kinetics? What structure-activity relationships exist for GHRH analogs? How does DPP-4 resistance translate to extended receptor occupancy?

cAMP Signaling Assays

Analysis of adenylyl cyclase activation and downstream pathways:

Downstream Readouts: CREB phosphorylation (Ser133), GH gene transcription (qPCR), and GH secretion (RIA, ELISA).

Structure-Activity Relationship Studies

Comparative analysis of GHRH analogs in research:

• Parameters: Receptor binding affinity, potency (EC50), efficacy (maximal response), metabolic stability
• Comparisons: Native GHRH, Sermorelin, various substituted analogs, DPP-4-sensitive vs. resistant variants

Pituitary Function Models

Investigation of somatotroph physiology. Consequently, model systems include:

• Primary pituitary cell cultures
• GH3 cell line (rat pituitary tumor)
• Perfused pituitary preparations
• In vivo pituitary function testing

Measured Parameters: GH release kinetics, desensitization/tachyphylaxis, receptor internalization, and feedback regulation mechanisms.

Pharmacokinetic Studies

Peptide stability and distribution analysis. Specifically:

• Plasma half-life determination
• DPP-4 degradation kinetics
• Tissue distribution patterns
• Modified vs. unmodified peptide comparisons

Pulsatile Dynamics Research

Studies requiring physiological release patterns:

• Acute signaling responses
• Receptor desensitization kinetics
• Intermittent vs. continuous occupancy effects
• Washout and recovery protocols

However, all applications remain strictly limited to controlled laboratory research environments.

ANALYTICAL VERIFICATION:

BIONIX CJC-1295 No DAC undergoes comprehensive analytical characterization:

• HPLC Analysis: ≥99% purity via reversed-phase gradient chromatography, separating sample components based on chemical interactions
• Mass Spectrometry: Exact molecular weight confirmation (3,367.9 Da) and sequence verification including D-Ala² modification
• D-Ala² Verification: Stereochemistry confirmation for DPP-4 resistance
• Additional Parameters: Amino acid composition, residual solvent testing, peptide content, endotoxin testing (LAL)

Physical Characteristics:

DEVELOPMENT STATUS:

CJC-1295 No DAC represents an established research tool for GHRH receptor studies:

• Discovery: 2005 (Jetté et al., tetrasubstituted analog design)
• Mechanism: Well-characterized Class B GPCR activation via Gs/cAMP pathway
• Clinical Status: Research compound; not approved for therapeutic use
• Regulatory Note: WADA prohibited substance (growth hormone secretagogue category)
• No DAC Rationale: Shorter half-life preserves physiological pulsatility essential for acute signaling studies
• DAC Distinction: DAC version (albumin-binding) is distinct compound with different pharmacokinetics
• Availability: BIONIX supplies exclusively for controlled laboratory research

Unlike the DAC variant, No DAC format enables investigation of pulsatile hormone dynamics. Consequently, researchers select this variant for acute signaling studies and pharmacokinetic analysis.

FREQUENTLY ENCOUNTERED INQUIRIES:

What distinguishes CJC-1295 No DAC from the DAC version? CJC-1295 No DAC lacks Drug Affinity Complex conjugation. Consequently, it exhibits a shorter half-life (~30 minutes vs. 5.8-9.2 days) and pulsatile release characteristics. Unlike the DAC version’s continuous receptor stimulation, No DAC more closely mimics natural GHRH release patterns. Therefore, No DAC is preferred for acute signaling studies, while DAC suits long-term exposure research.

How is this peptide used in laboratory research? Studies employ CJC-1295 No DAC to investigate GHRH receptor binding kinetics, adenylyl cyclase activation, and cAMP signaling pathways. Furthermore, researchers utilize it for structure-activity relationship studies comparing GHRH analogs, pituitary function models, and pharmacokinetic analysis of peptide stability.

What are the four amino acid substitutions? The tetrasubstituted structure contains: D-Alanine at position 2 (critical DPP-4 resistance), Glutamine at position 8 (deamidation protection), Alanine at position 15 (structural stability), and Leucine/Norleucine at position 27 (oxidation resistance). Specifically, the D-Ala² modification provides primary metabolic stability, extending half-life from ~7 minutes to ~30 minutes.

What storage conditions maintain stability? Lyophilized powder requires -20°C storage for long-term stability (up to 24 months). Additionally, protect from light and moisture. Furthermore, avoid repeated freeze-thaw cycles. Consequently, after reconstitution, store at 2-8°C and use within 2-4 weeks, or prepare aliquots and freeze for extended storage.

Why choose No DAC over DAC for research? No DAC is preferred for studies requiring precise control of pulsatile hormone dynamics, acute signaling responses, and receptor desensitization kinetics. Specifically, the shorter half-life allows cleaner washout between doses and more physiological receptor occupancy patterns. However, DAC variants better suit long-term exposure protocols and cumulative effect studies.

What is the mechanism of DPP-4 resistance? Native GHRH is rapidly cleaved between positions 2 and 3 by DPP-4. Consequently, the D-Ala² modification creates a stereochemical barrier preventing enzyme recognition. As a result, the peptide maintains structural integrity in plasma, extending research observation windows while preserving full GHRH receptor binding affinity.

REFERENCES:

• PMID: 15961554 — Jetté L et al., “Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor,” Endocrinology, 2005.
• PMID: 3531238 — Frohman LA et al., “Rapid enzymatic degradation of growth hormone-releasing hormone,” J Clin Invest, 1986.
• PMID: 12109870 — Izdebski J et al., “New potent hGH-RH analogues with increased resistance to enzymatic degradation,” J Pept Sci, 2002.
• PMID: 16352683 — Teichman SL et al., “Prolonged Stimulation of Growth Hormone by CJC-1295,” J Clin Endocrinol Metab, 2006.
• Mayo KE et al., “International Union of Pharmacology. XXXV. The glucagon receptor family,” Pharmacol Rev, 2003.