CJC-1295 No DAC (Modified GRF 1–29) – Research Compound Profile

CJC-1295 No DAC (Modified GRF 1–29) – Research Compound Profile

Category: Hormonal Research | Molecular Type: Synthetic 29-Amino-Acid Peptide (Modified GRF 1–29) | Research Status: Clinically Studied (GHRH Analog Class)

This page compiles published research data for qualified researchers. CJC-1295 No DAC (Modified GRF 1–29) is sold exclusively as a research compound, has not been approved by the FDA for human consumption, and is not intended for human use or self-administration. Nothing on this page constitutes medical advice, diagnosis, or a treatment recommendation.

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Molecular Overview

Important distinction: CJC-1295 No DAC — more precisely designated Modified GRF (1–29) or Mod GRF 1–29 — is not the same molecule as “CJC-1295 with DAC.” No Drug Affinity Complex (DAC) moiety is present in this product. The two are structurally related but pharmacokinetically distinct GHRH analogs, and published data on one should not be assumed to describe the other.

Mod GRF 1–29 is a truncated synthetic analog of human growth hormone-releasing hormone (GHRH). It comprises the first 29 amino acids of native GHRH (1–44) and incorporates four strategic amino acid substitutions: D-Ala at position 2, Gln at position 8, Ala at position 15, and Leu at position 27. These modifications were engineered to confer resistance to rapid enzymatic cleavage by dipeptidyl peptidase IV (DPP-IV) and other serum proteases while preserving full agonist activity at the GHRH receptor [1][2].

Because no DAC/albumin-binding moiety is attached, this no-DAC form retains a short plasma half-life on the order of tens of minutes, in contrast to the DAC-conjugated variant of CJC-1295, whose covalent albumin binding extends its elimination half-life to multiple days [1][4]. This brief duration of action produces discrete growth hormone (GH) pulses that more closely approximate the endogenous pulsatile secretory pattern than the sustained-albumin-bound form does. Native GHRH (1–44) has an even shorter plasma half-life, on the order of several minutes, rendering it impractical for research applications requiring more than acute stimulation; the four modifications in Mod GRF 1–29 extend functional activity sufficiently to stimulate robust GH release while still clearing before the next endogenous secretory cycle [2][7].

Clinical investigation of CJC-1295 with DAC — the long-acting, albumin-bound member of this analog family, discussed here for pharmacological context only — has documented a statistically significant, dose-dependent increase in mean plasma GH and IGF-1 in healthy adult subjects [1]. This finding is presented as supportive evidence that GHRH-receptor agonism within this peptide class reliably elevates the GH/IGF-1 axis; it does not describe the no-DAC product’s own pharmacokinetic duration, which is governed entirely by its short, unconjugated half-life.

Mechanism of Action

Upon administration, Mod GRF 1–29 enters the circulation and binds to GHRH receptors (GHRH-R) expressed on somatotroph cells of the anterior pituitary gland. GHRH-R belongs to the class B (secretin) family of G-protein-coupled receptors (GPCRs). Receptor activation initiates an intracellular signaling cascade involving cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), which in turn opens voltage-gated calcium channels. The resulting calcium influx drives exocytosis of stored GH vesicles from somatotroph granules [2][3][8].

Beyond acute GH release, GHRH-R activation also stimulates transcription of the GH gene (GH1) and promotes somatotroph cellular proliferation over time. Alba et al. (2006) demonstrated this trophic effect in GHRH knockout mice using CJC-1295 with DAC — the long-acting, albumin-conjugated GHRH analog, not the no-DAC product described on this page: chronic administration normalized body weight, body length, and pituitary GH mRNA levels, indicating that sustained GHRH-receptor stimulation can restore pituitary GH-secretory capacity [5]. This finding is cited here to illustrate the trophic consequences of GHRH-receptor agonism as a receptor class, not to describe the pharmacokinetics of Mod GRF 1–29 itself.

A pharmacologically significant distinction between GHRH analogs and exogenous recombinant human growth hormone (rhGH) is the preservation of the hypothalamic-pituitary negative-feedback loop. Somatostatin, released from the hypothalamus in response to rising GH levels, periodically inhibits further GH release, maintaining the natural pulsatile secretory pattern associated with physiologic outcomes [3]. Ionescu and Frohman (2006) confirmed, using CJC-1295 with DAC, that even continuous receptor stimulation by that long-acting variant maintained pulsatile GH secretion, demonstrating that the somatostatin-mediated feedback system was not overridden [3]. For the short-acting no-DAC variant described on this page, GH pulsatility is preserved as a direct and more straightforward consequence of its own rapid clearance: each administration event produces a single discrete GH pulse rather than a sustained plateau, without relying on somatostatin feedback to interrupt an otherwise continuous albumin-bound signal [7][8].

Additionally, GHRH analogs including Mod GRF 1–29 have been investigated in combination with growth hormone-releasing peptides (GHRPs) that act via the independent ghrelin/GHS-R1a receptor pathway. Published data indicate that the GHRH + GHRP combination exploits complementary, non-overlapping receptor mechanisms, producing a synergistic GH response that significantly exceeds the additive sum of either compound class alone [8][10].

Published Research Parameters

The following table indexes the study models, durations, and reported observations of selected peer-reviewed publications. Dose, frequency, and administration-route details are deliberately omitted. Where a study used CJC-1295 with DAC or native GHRH(1-44) rather than the no-DAC product itself, the compound is identified explicitly. This is a bibliographic index only — not a protocol and not a recommendation for any use.

Stability & Storage Characteristics

Published data and manufacturer specifications indicate the following stability parameters for GHRH-analog peptides of this class:

• Lyophilized (unreconstituted) stability: The lyophilized powder form demonstrates long-term stability when stored at −20 °C (−4 °F) for up to approximately 24 months. Short-term storage at 2–8 °C (35.6–46.4 °F) is generally acceptable for several months. Vials should remain sealed and protected from light and moisture [1].
• Reconstituted solution stability: Once reconstituted, peptide solutions of this class are generally stable at 2–8 °C (35.6–46.4 °F) for up to 4 weeks when protected from light. Freezing of reconstituted solutions is not recommended, as ice crystal formation can fragment peptide chains.
• Temperature sensitivity: GHRH-analog peptides are susceptible to thermal degradation. Repeated freeze-thaw cycling of reconstituted solutions should be avoided to preserve molecular integrity.
• Light sensitivity: As with most peptide compounds, storage in amber vials or opaque containers is recommended to minimize photodegradation.
• Reconstitution considerations: Published protocols note that gentle handling (swirling rather than vigorous agitation) during reconstitution is important for preserving peptide tertiary structure and avoiding denaturation or foaming [2].
• Degradation chemistry: The four DPP-IV-resistance substitutions in Mod GRF 1–29 remove the native dipeptidyl cleavage site but do not eliminate general peptide degradation risk. Deamidation of Gln or Asn-adjacent residues and oxidation at Met remain the principal chemical liabilities in solution over time, both accelerated by elevated temperature and pH extremes.

Analytical Characterization

Quality assessment of Mod GRF 1–29 relies on an orthogonal analytical panel standard for short synthetic peptides. Reverse-phase HPLC establishes purity and resolves deamidated or truncated synthesis-related impurities from the parent 29-residue sequence. Electrospray mass spectrometry (ESI-MS) confirms the intact monoisotopic mass and distinguishes the four-substitution Mod GRF 1–29 sequence from unmodified native GHRH fragments or from the DAC-conjugated form, which carries substantially higher mass due to the added linker and MPA moiety. A peptide-content assay quantifies net peptide mass independent of counter-ion, buffer salts, and residual moisture, since gravimetric lyophilizate weight alone is not a reliable purity indicator. Chiral/stereochemical purity confirmation is relevant given the multiple synthetic substitution steps involved in producing the four-residue-modified sequence. A complete quality assurance documentation should report all of these parameters independently for each production lot.

Key Published Research Findings

All findings below are derived from peer-reviewed publications. Each observation is attributed to its source study and, where relevant, to the specific compound studied (CJC-1295 with DAC, native GHRH, or the closely related short-acting analog Mod GRF 1–29 / CJC-1295 no DAC).

• Growth Hormone Elevation (CJC-1295 with DAC): In a 2006 randomized, placebo-controlled trial published in the Journal of Clinical Endocrinology & Metabolism, Teichman et al. reported that CJC-1295 with DAC in healthy adults produced a statistically significant, dose-dependent increase in mean plasma GH concentrations persisting for multiple days, with a sustained IGF-1 elevation over 9–11 days [1]. This study evaluated the long-acting, albumin-conjugated variant, not the no-DAC product on this page.

• Preserved Pulsatile Secretion (CJC-1295 with DAC): In a 2006 study published in the Journal of Clinical Endocrinology & Metabolism, Ionescu and Frohman demonstrated that pulsatile GH secretion was maintained even under continuous stimulation by CJC-1295 with DAC, indicating that the hypothalamic somatostatin feedback mechanism remained intact despite sustained receptor occupancy. This contrasts with exogenous rhGH administration, which delivers only the 22-kDa isoform in a non-physiologic bolus pattern [3].

• Pituitary Trophic Restoration in Knockout Models (CJC-1295 with DAC): In a 2006 study published in the American Journal of Physiology – Endocrinology and Metabolism, Alba et al. demonstrated that once-daily administration of CJC-1295 with DAC in GHRH knockout mice normalized body weight, body length, and pituitary GH mRNA expression. This finding suggests that chronic GHRH-receptor stimulation promotes somatotroph proliferation, a receptor-class-level effect distinct from the acute, short-duration signaling produced by the no-DAC product on this page [5].

• Endocrine and Metabolic Effects in Aged Subjects (short-acting GHRH 1–29 analog): Khorram et al. (1997) reported in the Journal of Clinical Endocrinology & Metabolism that long-term administration of [Nle²⁷]GRF 1–29-NH₂ — a closely related short-acting GHRH(1–29) analog, structurally analogous to the no-DAC product on this page — in age-advanced men and women produced measurable endocrine and metabolic effects, including a dose-dependent GH response [6].

• Body Composition Changes in Clinical Context: Salgado et al. (2020) reviewed published evidence in PMC indicating that GHRH-analog and growth hormone secretagogue administration as a class has been associated with reductions in visceral adipose tissue and increases in lean body mass in clinical research populations [11]. Similarly, Walker (2006) reviewed sermorelin data — sermorelin being another short-acting GHRH(1–29) analog closely related to the no-DAC product — in Clinical Interventions in Aging, noting improvements in body composition markers associated with this analog class [7].

• GH Pulsatility and Insulin Sensitivity: In a 2011 study published in PMC, Makimura et al. observed that a GHRH analog increased endogenous GH pulsatility and documented changes in insulin sensitivity parameters in healthy men [12].

• Serum Protein Profile Modulation (CJC-1295 with DAC): In a 2009 study published in Growth Hormone & IGF Research, Sackmann-Sala et al. reported that activation of the GH/IGF-1 axis by CJC-1295 with DAC resulted in measurable serum protein profile changes in normal adult subjects, providing biomarker evidence of systemic GH pathway activation attributable to the long-acting variant [13].

• Cognitive Function Investigation: Baker et al. (2013) examined the effects of GHRH administration on cognitive function in adults with mild cognitive impairment and healthy older adults, reporting findings that suggest GH-axis modulation may influence neurocognitive parameters [9].

• GH Augmentation in Elderly Via Continuous Infusion (native GHRH): Corpas et al. (1993) published in the Journal of Clinical Endocrinology & Metabolism that continuous infusion of native GHRH(1–44) for 14 days increased GH and IGF-1 levels in elderly men, supporting the concept that GHRH-receptor stimulation can augment the GH axis in aged populations with diminished endogenous secretion [15]. This study used unconjugated native GHRH(1–44), not the modified peptide described on this page.

Safety Profile in Published Literature

The GHRH-analog class has been consistently characterized as well tolerated in published clinical and preclinical research:

• Injection-site reactions: In clinical trials of CJC-1295 with DAC by Teichman et al. (2006), mild and transient redness, swelling, or itching at the injection site were the most commonly reported adverse events [1]. Sigalos and Pastuszak (2017) confirmed this finding in their review of growth hormone secretagogue safety data across the class [10].

• Transient flushing: Brief facial flushing or warmth following administration was noted in clinical studies of this analog class, particularly at initial exposures. This effect was attributed to transient vasodilation and was observed to diminish with repeated exposure [1][10].

• Headache: Occasional mild headache was reported in the Teichman et al. (2006) clinical trials, generally self-limiting in nature [1].

• Transient fluid retention: Mild peripheral edema was reported in some study subjects during early phases of GHRH-analog administration, consistent with known GH/IGF-1 axis activation effects. This finding was documented to resolve spontaneously in published reports [10][11].

• Glycemic considerations: Because GH can acutely antagonize insulin action, published literature notes the importance of monitoring glycemic parameters in research models, particularly those involving fasted-state experimental designs [8][13].

• Overall safety assessment: No serious adverse reactions were reported across the CJC-1295 (with DAC) randomized, placebo-controlled trials of Teichman et al. (2006) [1]. Sigalos and Pastuszak (2017) concluded in their comprehensive review that growth hormone secretagogues as a class demonstrated a favorable safety profile in published literature [10].

Regulatory Status

• FDA Approval: CJC-1295 No DAC (Modified GRF 1–29) has not been approved by the U.S. Food and Drug Administration (FDA) for any therapeutic indication in humans.
• Clinical Trial Activity: The GHRH-analog class (including the structurally related compounds tesamorelin, sermorelin, and CJC-1295 with DAC) has been the subject of multiple clinical trials. Tesamorelin (Egrifta®) has received FDA approval for a specific indication, while sermorelin was previously approved for diagnostic use. CJC-1295 with DAC has itself been studied in Phase I/II clinical settings, though CJC-1295 no DAC as a discrete product has not been independently taken through registered human trials [1][7].
• Research Classification: CJC-1295 No DAC is classified and sold as a research compound. It is not intended for human consumption, therapeutic use, or self-administration.
• Regulatory considerations: Researchers should ensure compliance with all applicable federal, state, and institutional regulations governing the acquisition, handling, and use of research peptides.

References

1. Journal of Clinical Endocrinology & Metabolism (2006) — 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. View Source

2. Endocrinology (2005) — Jetté L, Léger R, Thibaudeau K, et al. 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. View Source

3. Journal of Clinical Endocrinology & Metabolism (2006) — Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. View Source

4. Wikipedia — CJC-1295: structure, pharmacokinetics, and comparison of DAC vs. no-DAC variants. View Source

5. American Journal of Physiology – Endocrinology and Metabolism (2006) — Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting GHRH analog, normalizes growth in the GHRH knockout mouse. View Source

6. Journal of Clinical Endocrinology & Metabolism (1997) — Khorram O, Laughlin GA, Yen SS. Endocrine and metabolic effects of long-term administration of [Nle27]growth hormone-releasing hormone-(1-29)-NH2 in age-advanced men and women. View Source

7. Clinical Interventions in Aging (2006) — Walker RF. Sermorelin: a better approach to management of adult-onset growth hormone insufficiency? View Source

8. Pharmacology & Therapeutics (2010) — Chapter MC, White CM, DeRidder A, et al. Chemical modification of class II G protein-coupled receptor ligands: frontiers in the development of peptide analogs as neuroendocrine pharmacological therapies. View Source

9. PMC (2013) — Baker LD, Barsness SM, Borber S, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults. View Source

10. PMC (2017) — Sigalos JT, Pastuszak AW. The safety and efficacy of growth hormone secretagogues. View Source

11. PMC (2020) — Salgado AL, et al. Beyond the androgen receptor: the role of growth hormone secretagogues in body composition in hypogonadal males. View Source

12. PMC (2011) — Makimura H, et al. Effects of a growth hormone-releasing hormone analog on endogenous GH pulsatility and insulin sensitivity in healthy men. View Source

13. Growth Hormone & IGF Research (2009) — Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. View Source

15. Journal of Clinical Endocrinology & Metabolism (1993) — Corpas E, Harman SM, Piñeyro MA, et al. Continuous subcutaneous infusions of growth hormone releasing hormone 1-44 for 14 days increase GH and insulin-like growth factor-I levels in old men. View Source

⚠️ Disclaimer: This page is provided for educational and informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations. CJC-1295 No DAC (Modified GRF 1–29) does not contain a Drug Affinity Complex and is a distinct compound from CJC-1295 with DAC. It is sold exclusively as a research compound and has not been approved by the FDA for human consumption or use. All information is derived from published peer-reviewed literature. Research must comply with all applicable laws, regulations, and institutional guidelines.

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