CJC-1295 No DAC (Mod GRF 1-29)

Mechanism of Action

Receptor Interaction

Modified GRF (1-29) interacts with the growth hormone-releasing hormone receptor (GHRHR), a class B G protein-coupled receptor (GPCR) located primarily on somatotropic cells in the anterior pituitary gland. Upon binding, the peptide induces a conformational change in the receptor that activates intracellular signaling cascades.

Signal Transduction Pathway

The primary signaling mechanism involves:

1. Gₛ Protein Activation: GHRHR coupling to stimulatory G proteins (Gₛ)
2. Adenylate Cyclase Stimulation: Activated Gₛ stimulates adenylate cyclase enzyme activity
3. cAMP Production: Adenylate cyclase converts ATP to cyclic adenosine monophosphate (cAMP)
4. PKA Activation: Elevated cAMP activates protein kinase A (PKA)
5. CREB Phosphorylation: PKA phosphorylates cAMP response element-binding protein (CREB)
6. Gene Transcription: Phosphorylated CREB promotes transcription of growth hormone genes

Pulsatile Secretion Pattern

Due to its short half-life (~30 minutes), Modified GRF (1-29) produces a transient spike in growth hormone release that closely mimics the body's natural pulsatile secretion pattern. This is in contrast to the sustained elevation produced by DAC-modified variants, making it particularly useful for research studying physiological GH dynamics.

Synergy with Growth Hormone Secretagogues

Modified GRF (1-29) is frequently studied in combination with growth hormone secretagogues (GHS) such as Ipamorelin, GHRP-2, or GHRP-6. These compounds act through different mechanisms:

• Modified GRF (1-29): Stimulates GH release via GHRHR activation
• GHS (e.g., Ipamorelin): Stimulates GH release via ghrelin receptor activation
• Synergistic Effect: Dual pathway activation produces amplified GH secretion compared to either compound alone

Enzymatic Stability

The strategic amino acid substitutions in Modified GRF (1-29) confer resistance to enzymatic degradation:

• DPP-IV Resistance: D-Alanine at position 2 prevents cleavage by dipeptidyl peptidase-IV
• Deamidation Prevention: Glutamine at position 8 eliminates asparagine deamidation
• Carboxypeptidase Protection: C-terminal amidation blocks carboxypeptidase activity

These modifications extend the peptide's functional half-life from seconds (native GHRH) to approximately 30 minutes, allowing sufficient time for receptor binding and signal transduction while maintaining pulsatile kinetics.

Research Applications

Endocrine Research

Modified GRF (1-29) serves as a valuable tool for investigating growth hormone regulation and pituitary function in controlled experimental settings:

• GHRH receptor binding affinity and kinetics assays
• Growth hormone secretion dynamics and pulsatility studies
• Somatotroph cell function and responsiveness evaluation
• Hypothalamic-pituitary axis regulation mechanisms

Peptide Pharmacology Studies

The compound is used to explore structure-activity relationships and pharmacokinetic properties:

• Comparative potency analysis among GHRH analogs
• Receptor specificity and selectivity profiling
• Dose-response curve characterization
• Peptide stability and degradation pathway analysis
• Bioavailability and distribution studies in animal models

Combination Therapy Research

Modified GRF (1-29) is frequently studied in combination with growth hormone secretagogues to investigate synergistic mechanisms:

• Mod GRF + Ipamorelin: Most commonly studied combination for amplified GH release
• Mod GRF + GHRP-2: Investigation of dual pathway activation
• Mod GRF + GHRP-6: Studies on appetite regulation and GH secretion
• Mod GRF + Hexarelin: Cardiac and neuroprotective research applications

Cell Signaling Research

In vitro cellular studies utilize Modified GRF (1-29) to examine intracellular signaling cascades:

• Adenylate cyclase activation and cAMP production measurement
• Protein kinase A (PKA) phosphorylation events
• CREB transcription factor activation
• Calcium mobilization and ion channel modulation
• Gene expression profiling following GHRHR activation

Animal Model Studies

Preclinical research in animal models has examined various endpoints:

• Growth hormone and IGF-1 plasma concentration changes
• Body composition alterations (lean mass vs. adipose tissue)
• Metabolic rate and energy expenditure measurements
• Sleep architecture and slow-wave sleep modulation
• Tissue repair and regeneration processes

Comparative Studies: DAC vs. No DAC

Research comparing Modified GRF (1-29) with CJC-1295 DAC has revealed distinct pharmacological profiles:

Parameter	Modified GRF (1-29) - No DAC	CJC-1295 with DAC
Half-Life	~30 minutes	~6-8 days
Dosing Frequency	2-3 times daily	Once or twice weekly
GH Release Pattern	Pulsatile (physiological)	Sustained elevation
Peak GH Levels	Higher acute peaks	Lower but sustained
Clearance	Rapid	Slow

Research Dosing Parameters

Reconstitution Guidelines

Modified GRF (1-29) is supplied as a lyophilized powder and must be reconstituted before use in research protocols:

• Reconstitution Solution: Bacteriostatic water or sterile water for injection
• Typical Concentration: 2mg peptide reconstituted in 2mL solution = 1mg/mL (1000mcg/mL)
• Mixing Technique: Gently swirl; do not shake vigorously to prevent peptide degradation
• Storage After Reconstitution: Refrigerate at 2-8°C; use within 14 days for optimal stability

Typical Research Dosing Ranges

Published preclinical studies have utilized various dosing protocols. The following ranges are commonly reported in scientific literature:

In Vitro Cell Culture Studies

• Concentration Range: 10 nM to 1 μM
• Typical Working Concentration: 100 nM
• Incubation Time: 15 minutes to 24 hours depending on endpoint

In Vivo Animal Model Studies (Rodents)

• Dose Range: 50-300 mcg per administration
• Common Dose: 100 mcg per injection
• Frequency: 2-3 times daily (morning, afternoon, evening)
• Route: Subcutaneous injection
• Timing: Often administered before meals or at bedtime

Combination Protocols (Mod GRF + GHS)

When studied in combination with growth hormone secretagogues:

• Modified GRF (1-29): 100 mcg
• + Ipamorelin: 100-200 mcg
• Frequency: 2-3 times daily
• Note: Co-administration produces synergistic GH release

Dosing Timing Considerations

Due to the short half-life of Modified GRF (1-29), timing of administration is critical in research protocols:

• Morning Dose: Upon waking (fasted state)
• Post-Exercise: Immediately following physical activity
• Evening Dose: Before bedtime to coincide with natural GH pulse
• Fasting State: Administration during fasted periods may enhance GH response

Storage and Stability

Form	Storage Condition	Stability Duration
Lyophilized Powder	-20°C (freezer)	2-3 years
Lyophilized Powder	2-8°C (refrigerator)	6-12 months
Reconstituted Solution	2-8°C (refrigerator)	14 days
Reconstituted Solution	-20°C (freezer)	30 days (single freeze only)

Handling Precautions

• Avoid repeated freeze-thaw cycles
• Protect from direct light exposure
• Use sterile technique for all reconstitution procedures
• Allow vial to reach room temperature before reconstitution
• Do not use if solution appears cloudy or contains particulates

Safety Profile & Research Observations

Preclinical Safety Observations

Animal model studies have generally reported Modified GRF (1-29) to be well-tolerated at research doses. The following observations have been documented in scientific literature:

Commonly Reported Effects in Animal Studies

• Injection Site Reactions: Mild erythema or swelling at subcutaneous injection sites (transient)
• Increased Appetite: Particularly when combined with ghrelin receptor agonists
• Water Retention: Mild fluid retention observed in some animal models
• Lethargy: Temporary drowsiness following administration (dose-dependent)

Less Common Observations

• Transient hyperglycemia (elevated blood glucose)
• Joint discomfort or stiffness
• Numbness or tingling in extremities
• Headache or pressure sensation

Contraindications in Research Models

Modified GRF (1-29) should not be used in research models with the following conditions:

• Active Malignancy: GH stimulation may promote tumor growth in cancer models
• Diabetic Models: May exacerbate insulin resistance and glucose dysregulation
• Pituitary Tumor Models: Risk of tumor growth stimulation
• Pregnancy/Lactation Models: Effects on fetal development not well-characterized

Drug Interactions in Research Settings

Potential interactions observed in preclinical studies:

• Insulin/Hypoglycemic Agents: May alter glucose homeostasis
• Corticosteroids: May reduce GH response to GHRH stimulation
• Thyroid Hormones: May influence GH secretion dynamics
• Somatostatin Analogs: Antagonistic effects on GH release

Monitoring Parameters in Research Protocols

When conducting research with Modified GRF (1-29), the following parameters are commonly monitored:

• Growth hormone and IGF-1 serum concentrations
• Fasting glucose and insulin levels
• Thyroid function markers (T3, T4, TSH)
• Cortisol levels
• Body composition measurements
• Injection site examination

Comparison: Modified GRF vs. CJC-1295 DAC Safety Profile

Aspect	Modified GRF (No DAC)	CJC-1295 with DAC
Injection Frequency	2-3x daily	1-2x weekly
GH Elevation Pattern	Pulsatile (physiological)	Sustained (non-physiological)
Injection Site Reactions	More frequent (due to dosing)	Less frequent
Desensitization Risk	Lower (pulsatile pattern)	Higher (sustained elevation)
Prolactin Elevation	Minimal	More pronounced

Long-Term Research Considerations

Extended duration studies (>6 months) in animal models have examined:

• Receptor Desensitization: Minimal with pulsatile dosing pattern
• Pituitary Function: No evidence of suppression with appropriate dosing
• Metabolic Effects: Generally favorable impact on body composition
• Tissue Changes: No pathological alterations observed at research doses

Quality Control & Purity

Safety in research applications depends on peptide purity and quality:

• Purity Standard: ≥99% by HPLC
• Endotoxin Level: <1.0 EU/mg
• Sterility: Tested and certified
• Heavy Metals: Below detection limits

Frequently Asked Questions

What is the difference between CJC-1295 with DAC and CJC-1295 No DAC?

CJC-1295 with DAC contains a Drug Affinity Complex that binds to albumin, extending its half-life to approximately 6-8 days. CJC-1295 No DAC (Modified GRF 1-29) lacks this modification, resulting in a much shorter half-life of ~30 minutes. This leads to different dosing schedules and GH release patterns: No DAC produces pulsatile release (2-3x daily dosing) while DAC produces sustained elevation (1-2x weekly dosing).

Why is Modified GRF (1-29) preferred over native GHRH?

Native GHRH has an extremely short half-life of only a few seconds due to rapid enzymatic degradation. Modified GRF (1-29) incorporates four strategic amino acid substitutions that confer resistance to enzymatic cleavage, extending the functional half-life to ~30 minutes while maintaining the natural pulsatile release pattern.

What is the optimal research dosing frequency?

Due to its short half-life, Modified GRF (1-29) is typically administered 2-3 times daily in research protocols. Common timing includes: (1) morning upon waking, (2) post-exercise or mid-afternoon, and (3) before bedtime. This mimics the body's natural pulsatile GH secretion pattern.

Can Modified GRF (1-29) be combined with other research peptides?

Yes, Modified GRF (1-29) is frequently studied in combination with growth hormone secretagogues (GHS) such as Ipamorelin, GHRP-2, or GHRP-6. These combinations produce synergistic effects because they activate GH release through different receptor pathways (GHRHR vs. ghrelin receptor), resulting in amplified GH secretion compared to either compound alone.

How should Modified GRF (1-29) be reconstituted?

The lyophilized powder should be reconstituted with bacteriostatic water or sterile water for injection. A typical protocol is to add 2mL of reconstitution solution to a 2mg vial, yielding a 1mg/mL (1000mcg/mL) concentration. Gently swirl the vial; do not shake vigorously. Store reconstituted solution at 2-8°C and use within 14 days.

What is the shelf life of lyophilized Modified GRF (1-29)?

When stored properly at -20°C (freezer), lyophilized Modified GRF (1-29) maintains stability for 2-3 years. If stored at 2-8°C (refrigerator), stability is approximately 6-12 months. Once reconstituted, the solution should be used within 14 days when refrigerated.

Does Modified GRF (1-29) cause receptor desensitization?

Research suggests that Modified GRF (1-29) has a lower risk of receptor desensitization compared to DAC-modified variants. This is because the short half-life produces pulsatile GH release that more closely mimics natural physiological patterns, allowing time for receptor recovery between doses. Sustained elevation (as with DAC versions) may increase desensitization risk over time.

What purity level should be expected?

Research-grade Modified GRF (1-29) should have a minimum purity of ≥99% as verified by High-Performance Liquid Chromatography (HPLC). Each batch should also undergo mass spectrometry for molecular weight confirmation and endotoxin testing (<1.0 EU/mg). Always request third-party testing certificates to verify quality.

Is Modified GRF (1-29) the same as Sermorelin?

No. Sermorelin is the acetate salt of GHRH(1-29) without the stabilizing amino acid substitutions. Modified GRF (1-29) contains four strategic substitutions (D-Ala², Gln⁸, Ala¹⁵, Leu²⁷) that significantly enhance resistance to enzymatic degradation, making it more stable and longer-lasting than Sermorelin in research applications.

What are the typical research endpoints measured?

Common research endpoints include: (1) serum growth hormone and IGF-1 concentrations, (2) body composition changes (lean mass vs. adipose tissue), (3) metabolic parameters (glucose, insulin sensitivity), (4) sleep quality and architecture, (5) tissue repair and regeneration markers, and (6) receptor binding affinity and signaling cascade activation.

Can Modified GRF (1-29) be used in cell culture studies?

Yes, Modified GRF (1-29) is commonly used in in-vitro cell culture studies, particularly with pituitary somatotroph cell lines. Typical working concentrations range from 10 nM to 1 μM, with 100 nM being a common starting point. It is used to study GHRHR activation, cAMP signaling, and gene expression changes.

What is the molecular weight of Modified GRF (1-29)?

The molecular weight of Modified GRF (1-29) is 3368.7 g/mol. This can be verified by mass spectrometry analysis, which should be included in the Certificate of Analysis (COA) provided with each batch.

Preclinical Research Summary

Growth Hormone Secretion Studies

Study Type: In vivo animal models (rodents, primates)

Key Findings:

• Modified GRF (1-29) produced dose-dependent increases in serum growth hormone levels
• Peak GH levels occurred 15-30 minutes post-administration
• GH levels returned to baseline within 2-3 hours, consistent with pulsatile secretion pattern
• Repeated dosing (2-3x daily) maintained physiological pulsatility without receptor desensitization

Reference: Jetté L, et al. "Human Growth Hormone-Releasing Factor (hGRF)1–29-Albumin Bioconjugates Activate the GRF Receptor on the Anterior Pituitary in Rats." Endocrinology, 2005;146(7):3052-3058.

Enzymatic Stability Research

Study Type: In vitro plasma stability assays

Key Findings:

• Native GHRH degraded within seconds when exposed to plasma enzymes
• Modified GRF (1-29) demonstrated >100-fold increased stability compared to native GHRH
• D-Alanine substitution at position 2 conferred resistance to dipeptidyl peptidase-IV (DPP-IV)
• C-terminal amidation protected against carboxypeptidase degradation

Reference: Frohman LA, et al. "Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo." J Clin Invest, 1986;78(4):906-913.

Receptor Binding and Affinity Studies

Study Type: In vitro receptor binding assays

Key Findings:

• Modified GRF (1-29) demonstrated high affinity for GHRH receptors (Kd ~1-5 nM)
• Binding affinity was comparable to or slightly enhanced compared to native GHRH
• Amino acid substitutions did not compromise receptor recognition
• Receptor activation led to robust adenylate cyclase stimulation and cAMP production

Reference: Izdebski J, et al. "New potent hGH-RH analogues with increased resistance to enzymatic degradation." J Pept Sci, 2002;8(7):289-296.

Combination Therapy Research (Mod GRF + Ipamorelin)

Study Type: In vivo animal models

Key Findings:

• Co-administration of Modified GRF (1-29) and Ipamorelin produced synergistic GH release
• Combined treatment resulted in 3-5x greater GH elevation compared to either compound alone
• Synergy attributed to dual pathway activation (GHRHR + ghrelin receptor)
• No evidence of receptor desensitization with repeated combination dosing

Body Composition Studies

Study Type: Long-term animal model studies (12-24 weeks)

Key Findings:

• Increased lean body mass (muscle tissue) in treated groups
• Decreased adipose tissue (body fat) compared to controls
• Improved muscle-to-fat ratio without changes in total body weight
• Effects were dose-dependent and reversible upon cessation

Metabolic Parameter Studies

Study Type: In vivo metabolic profiling

Key Findings:

• Elevated serum IGF-1 levels (secondary to GH increase)
• Improved insulin sensitivity in some animal models
• Increased lipolysis (fat breakdown) and fatty acid oxidation
• Enhanced protein synthesis and nitrogen retention

Sleep and Recovery Research

Study Type: Sleep architecture analysis in animal models

Key Findings:

• Evening administration enhanced slow-wave sleep (SWS) duration
• Increased sleep quality markers (delta wave activity)
• Synergy with natural nocturnal GH pulse
• Potential implications for tissue repair and recovery processes

Comparative Studies: DAC vs. No DAC

Study Type: Head-to-head comparison in rodent models

Key Findings:

• Modified GRF (No DAC): Produced higher peak GH levels but shorter duration
• CJC-1295 with DAC: Produced lower peak GH but sustained elevation over days
• Pulsatility: No DAC maintained physiological pulsatile pattern; DAC produced non-physiological sustained elevation
• Prolactin: No DAC had minimal effect on prolactin; DAC caused sustained prolactin elevation
• Desensitization: No DAC showed less receptor desensitization over time

Safety and Tolerability Studies

Study Type: Long-term toxicology studies in animal models

Key Findings:

• No evidence of organ toxicity at research doses
• No pathological changes in pituitary tissue
• Minimal injection site reactions (mild, transient)
• No adverse effects on reproductive function
• Reversibility: All effects reversed upon treatment cessation

Tissue Repair and Regeneration Research

Study Type: Injury models in rodents

Key Findings:

• Accelerated wound healing in dermal injury models
• Enhanced muscle regeneration following induced injury
• Improved bone density markers in osteopenia models
• Potential neuroprotective effects in CNS injury models

Key Scientific References

1. Jetté L, et al. Endocrinology. 2005;146(7):3052-3058.
2. Frohman LA, et al. J Clin Invest. 1986;78(4):906-913.
3. Izdebski J, et al. J Pept Sci. 2002;8(7):289-296.
4. Momany FA, et al. Endocrinology. 1981;108(1):31-39.
5. Teichman SL, et al. Growth Horm IGF Res. 2006;16(5-6):321-328.

Scientific References & Citations

Primary Research Articles

GHRH Receptor and Signaling

Combination Therapy Research

Body Composition and Metabolic Effects

Review Articles

Additional Resources

• PubChem: Compound Database
• UniProt: Protein Sequence and Functional Information
• NCBI Peptide Database: Peptide Sequences
• DrugBank: Drug and Peptide Information

Third-Party Testing & Quality Assurance

Every batch of Modified GRF (1-29) undergoes comprehensive third-party testing to ensure the highest quality standards for research applications. We are committed to transparency and provide detailed analytical testing results for each product lot.

Analytical Testing Methods

Certificate of Analysis (COA)

Each batch is accompanied by a Certificate of Analysis that includes:

• Batch/Lot Number: Unique identifier for traceability
• Manufacturing Date: Date of production
• Expiration Date: Recommended use-by date
• HPLC Chromatogram: Visual purity profile
• Mass Spectrum: Molecular weight confirmation
• Purity Percentage: Quantified by HPLC (≥99%)
• Endotoxin Level: LAL assay results (<1.0 EU/mg)
• Sterility Results: Pass/Fail determination
• Storage Recommendations: Optimal storage conditions

Quality Control Standards

Parameter	Specification	Test Method
Appearance	White to off-white lyophilized powder	Visual inspection
Purity (HPLC)	≥99.0%	RP-HPLC
Molecular Weight	3368.7 ± 1.0 g/mol	ESI-MS
Endotoxin	<1.0 EU/mg	LAL Assay
Sterility	No growth	USP <71>
Water Content	<5.0%	Karl Fischer
Peptide Content	≥95.0%	Amino Acid Analysis

Manufacturing Standards

Modified GRF (1-29) is manufactured under controlled laboratory conditions following Good Manufacturing Practices (GMP) guidelines:

• Solid-Phase Peptide Synthesis (SPPS): Fmoc chemistry for precise sequence assembly
• Purification: Preparative HPLC to remove impurities and truncated sequences
• Lyophilization: Freeze-drying to ensure stability and extended shelf life
• Quality Control: Batch testing before release
• Storage: Maintained at -20°C until shipment

Requesting COA Documents

To request a Certificate of Analysis for your specific batch:

1. Locate the batch/lot number on your product vial label
2. Contact our customer support team with the batch number
3. COA will be provided in PDF format within 24-48 hours