CJC-1295 No DAC (Modified GRF 1-29) — Mechanism, Research & Limitations

This article is for informational and educational purposes only and does not constitute medical advice. CJC-1295 No DAC is supplied by Wholesale Peps as lyophilized research-grade material for in vitro laboratory use only and is not approved by the FDA for human or veterinary use.

Wholesale Peps is not affiliated with, endorsed by, or in any way connected to ConjuChem Biotechnologies. This research review is compiled from publicly available peer-reviewed literature for educational purposes only.

Research Summary

CJC-1295 No DAC (also referred to as Modified GRF 1-29) is a synthetic 29-amino-acid analogue of growth hormone-releasing hormone (GHRH) incorporating four targeted amino acid substitutions relative to native GRF(1-29): D-Ala at position 2 to resist DPP-IV cleavage, Gln at position 8 to prevent asparagine deamidation, Ala at position 15 to enhance alpha-helical stability, and Nle at position 27 to eliminate methionine oxidation susceptibility. Acting as an agonist at the pituitary growth hormone-releasing hormone receptor (GHRHR), it stimulates pulsatile GH release and downstream IGF-1 elevation through the same receptor pathway as native GHRH, Sermorelin, and tesamorelin. The “No DAC” designation distinguishes it from CJC-1295 with DAC — a related analogue bearing albumin-binding chemistry that extends biological half-life to approximately 7–8 days — by a substantially shorter plasma half-life and the absence of covalent albumin modification. No regulatory approval has been granted for CJC-1295 No DAC in any jurisdiction. Published controlled clinical data specific to the No DAC form are limited; the most substantial human pharmacology evidence for this structural series derives from a Phase 1 trial of CJC-1295 with DAC (Teichman et al., 2006). CJC-1295 No DAC is among the better-characterized modified GRF(1-29) analogues in the published peptide pharmacology literature.

1. Background

1.1 Native GHRH and the Biological Basis of GRF(1-29)

Growth hormone-releasing hormone (GHRH) is a 44-amino-acid hypothalamic neuropeptide that acts at pituitary somatotroph cells to stimulate the synthesis and pulsatile secretion of growth hormone (GH). Its endogenous role is to coordinate GH pulsatility in concert with somatostatin, the inhibitory counterpart that suppresses GH release between pulses. Structure-activity relationship studies conducted in the 1980s established that the full biological activity of native GHRH is retained within its first 29 amino acids — the truncated form designated GRF(1-29). This finding is foundational to the GHRH analogue class: the remaining 15 C-terminal residues of native GHRH are generally considered less important for receptor activation than the N-terminal 29 residues, and GRF(1-29) analogues can engage the GHRHR with full agonist potency [3].

Sermorelin, the acetate salt of native GRF(1-29), was subsequently developed as a pharmaceutical agent and received regulatory approval for evaluation of GH reserve in pediatric growth hormone deficiency, making it one of the few GRF(1-29) analogues to reach clinical use. However, native GRF(1-29) is subject to rapid enzymatic degradation in plasma — a limitation that motivated the development of stability-enhanced analogues including Modified GRF(1-29).

1.2 DPP-IV Degradation and the Four-Modification Rationale

The primary pharmacokinetic obstacle for native GRF(1-29)/Sermorelin is rapid cleavage by dipeptidyl peptidase IV (DPP-IV), a ubiquitous serine protease that removes the N-terminal Tyr¹–Ala² dipeptide from GRF peptides. Frohman et al. (1989) demonstrated that DPP-IV is the principal enzyme responsible for rapid GRF degradation in human plasma, with the resulting GRF(3-29) cleavage product essentially devoid of GH-releasing activity [2]. Under physiological conditions, native GRF(1-29) has a plasma half-life of approximately 2–3 minutes following administration — insufficient duration for many research applications.

Modified GRF(1-29) addresses this through four targeted substitutions. D-Ala at position 2 is the critical modification: DPP-IV requires a stereospecific L-amino acid at the scissile bond position, and D-Ala eliminates recognition, protecting the Tyr¹–D-Ala² bond from cleavage. The remaining three modifications address distinct secondary vulnerabilities in the native sequence: Gln at position 8 replaces the deamidation-prone Asn residue; Ala at position 15 replaces Gly to reduce backbone flexibility and enhance alpha-helical character; and norleucine (Nle) at position 27 replaces Met to eliminate methionine oxidation, a common source of peptide degradation under ambient conditions. Together these four modifications improve both enzymatic and chemical stability relative to the native GRF(1-29) sequence.

1.3 ConjuChem Biotechnologies and the “No DAC” Distinction

ConjuChem Biotechnologies (Montreal, Canada) developed the Drug Affinity Complex (DAC) technology platform, which uses a maleimide-modified propionic acid group attached to a lysine residue to form a stable covalent bond with Cys-34 on circulating serum albumin. Because albumin has a half-life of approximately 19 days in humans, peptides conjugated to albumin via this technology acquire dramatically extended biological half-lives. CJC-1295 refers to Modified GRF(1-29) incorporating the full DAC chemistry, with a plasma half-life of approximately 7–8 days as reported in Phase 1 clinical trials [1]. CJC-1295 No DAC — also called Modified GRF 1-29 or Mod GRF(1-29) — retains the four stability modifications but lacks the albumin-binding chemistry entirely, resulting in a substantially shorter plasma half-life. In research and commercial contexts, “CJC-1295” is sometimes used without specifying whether DAC is present or absent, which can create ambiguity about which compound is being discussed.

2. Molecular Structure

CJC-1295 No DAC is a 29-amino-acid peptide derived from the native GHRH(1-29) sequence with four amino acid substitutions at positions 2, 8, 15, and 27. At 29 residues and approximately 3,368 Da, it is substantially larger than the small-molecule GHSRPs and pentapeptides such as ipamorelin, and its structural properties are most clearly conveyed by a modification comparison table rather than individual residue display.

Table 1 — Sequence Modifications: Native GRF(1-29) vs. CJC-1295 No DAC
Position	Native GRF(1-29) Residue	CJC-1295 No DAC Residue	Chemical Rationale
2	Ala (L-alanine)	D-Ala (D-alanine)	Eliminates DPP-IV recognition at Tyr¹–Ala² scissile bond; primary stability modification
8	Asn (asparagine)	Gln (glutamine)	Prevents asparagine deamidation; Asn is prone to conversion to Asp under physiological conditions
15	Gly (glycine)	Ala (alanine)	Replaces achiral, flexible Gly with Ala; enhances alpha-helical stability and receptor interaction geometry
27	Met (methionine)	Nle (norleucine)	Eliminates methionine oxidation; Nle is an isosteric replacement lacking the oxidation-susceptible sulfur
All others (1, 3–7, 9–14, 16–26, 28–29)	Conserved from native GRF(1-29) sequence		Biological activity, receptor binding geometry, and N-terminal pharmacophore preserved

Table 2 — CJC-1295 No DAC Structural Properties
Property	Detail
Full name	Modified GRF(1-29); Mod GRF 1-29; CJC-1295 without DAC
Peptide length	29 amino acids
Key modifications	D-Ala², Gln&sup8;, Ala¹&sup5;, Nle²&sup7;
Molecular weight	~3,368 Da
C-terminus	Amide (–NH₂)
Primary target	GHRHR (growth hormone-releasing hormone receptor; class B GPCR)
Developer	ConjuChem Biotechnologies (Montreal, Canada)
Related compounds	Sermorelin (native GRF 1-29), CJC-1295 with DAC, Tesamorelin (44 aa GHRH analogue)

3. Mechanism of Action

Pituitary

GHRHR Agonism and GH Pulse Induction

CJC-1295 No DAC binds and activates the pituitary GHRHR, a class B G-protein-coupled receptor coupled to Gαs. Receptor activation stimulates adenylyl cyclase, raising intracellular cAMP, activating PKA, and driving exocytosis of stored GH granules from somatotroph cells. This is the same cAMP-mediated pathway activated by native GHRH, Sermorelin, and tesamorelin. The resulting GH release is pulsatile in character, with somatostatin feedback limiting pulse duration and magnitude.

Stability

DPP-IV Resistance and Enzymatic Stability

The D-Ala substitution at position 2 eliminates the stereospecific DPP-IV cleavage site at the Tyr¹–Ala² bond, the primary degradation pathway for native GRF(1-29) in plasma. This single modification is responsible for the principal improvement in plasma persistence relative to Sermorelin. The additional modifications at positions 8, 15, and 27 address chemical degradation pathways (deamidation, conformational instability, and oxidation) rather than enzymatic cleavage, contributing to overall compound integrity during storage and in physiological environments.

Systemic

Pulsatile GH Release and IGF-1 Elevation

GH pulses produced by GHRHR agonism drive hepatic IGF-1 synthesis through the GH receptor–JAK2–STAT5b signaling cascade. Because CJC-1295 No DAC acts at the level of pituitary secretion rather than replacing GH directly, the hypothalamic somatostatin feedback axis remains at least partially intact, providing a degree of physiological regulation of GH output. The short plasma half-life of the No DAC form produces a GH pulse window more similar to Sermorelin than to the prolonged GH/IGF-1 elevation seen with CJC-1295 with DAC.

GHSR-1a Synergy

Complementary Pathway Amplification

GHRHR agonism (cAMP/PKA) and GHSR-1a agonism (calcium/PKC, as activated by ipamorelin and related peptides) engage mechanistically distinct intracellular pathways in pituitary somatotrophs. Co-stimulation of both pathways produces synergistic GH release substantially greater than either stimulus alone — the mechanistic basis for combining CJC-1295 No DAC with GHSR-1a agonists in research contexts. Controlled human data evaluating this specific combination for defined research endpoints have not been published in sufficient form to permit clinical inference.

4. Key Research Findings

4.1 GHRHR Pharmacology and the Native GHRH Evidence Base

The pharmacological framework underpinning CJC-1295 No DAC is grounded in decades of GHRH and GHRHR research. Frohman and Jansson (1986) provided a comprehensive review of GHRH biology, establishing the dose-response relationship for GH release, the structure-activity determinants of GRF(1-29) activity, and the receptor binding characteristics that define this peptide class [3]. This foundational pharmacology — confirmed through subsequent clinical development of Sermorelin and tesamorelin — establishes that the GHRHR agonism mechanism is operative in human subjects and that GRF(1-29)-based peptides retain full receptor affinity. CJC-1295 No DAC inherits this pharmacological profile through its conserved receptor-binding sequence, differing from Sermorelin only in the four stability-enhancing modifications.

4.2 CJC-1295 with DAC — Phase 1 Clinical Evidence

The most substantial published clinical pharmacology evidence for the CJC structural series derives from a Phase 1 dose-escalation trial of CJC-1295 with DAC conducted by Teichman et al. (2006) in healthy adult volunteers [1]. The study evaluated single and multiple subcutaneous doses of the DAC-bearing compound and reported dose-dependent, prolonged elevations in GH and IGF-1. Mean half-life of CJC-1295 (with DAC) was approximately 7–8 days, and IGF-1 levels remained elevated for up to 28 days following a single dose in some participants. GH responses were consistent with GHRHR agonism, and no serious adverse events were reported in this early-phase study.

This trial does not evaluate CJC-1295 No DAC specifically. However, it establishes that the Modified GRF(1-29) framework — incorporating the four stability modifications described in Section 2 — engages the GHRHR effectively in human subjects when adequate systemic exposure is maintained. The pharmacokinetic and pharmacodynamic profiles of the DAC and No DAC forms differ substantially, and findings from the DAC form cannot be extrapolated directly to the No DAC form.

Fig. 1 — Schematic Plasma Half-Life Comparison: GRF(1-29) Analogue Series (Not to Linear Scale)

Schematic comparison of approximate plasma half-lives across the GRF(1-29) analogue series. Bars are proportional to log-scale duration and are not to linear scale. Sermorelin half-life from Frohman et al. (1989) [2]; CJC-1295 with DAC half-life from Teichman et al. (2006) [1]. *CJC-1295 No DAC half-life is an estimate based on DPP-IV protection conferred by D-Ala² substitution; formal human pharmacokinetic data for this compound have not been published in peer-reviewed literature as of the review date.

Note on Evidence Scope: Sections 4.3 and 4.4 discuss DPP-IV degradation studies and the Sermorelin clinical context. These inform the biochemical rationale for Modified GRF(1-29) but do not constitute direct clinical evidence for CJC-1295 No DAC.

4.3 DPP-IV Degradation and the Stability Evidence Base

Frohman et al. (1989) characterized DPP-IV as the principal enzyme responsible for rapid GRF peptide degradation in human plasma, demonstrating that the Tyr¹–Ala² dipeptide is the primary cleavage product and that the resulting GRF(3-29) fragment has negligible GH-releasing activity [2]. This work established the biochemical rationale for stereospecific amino acid substitution at position 2 as a stability strategy and underpins the expected plasma persistence advantage of Modified GRF(1-29) over native Sermorelin. Published formal pharmacokinetic characterization of CJC-1295 No DAC specifically — measuring plasma peptide concentrations, half-life, and metabolic clearance routes in human subjects — has not been identified in the peer-reviewed literature as of the review date.

4.4 Sermorelin as Clinical Reference

Sermorelin (native GRF 1-29) received FDA approval in 1997 for assessment of GH reserve in children with suspected growth hormone deficiency and was used in clinical practice through its voluntary US market withdrawal in 2008. Walker (2006) discussed Sermorelin in the context of adult-onset growth hormone insufficiency, noting its potential as an approach to stimulating endogenous GH secretion as an alternative to exogenous GH replacement [4]. The clinical experience with Sermorelin confirms that GRF(1-29)-based GHRHR agonism produces measurable GH and IGF-1 responses in human subjects and informs the pharmacological framework applicable to Modified GRF analogues — though direct pharmacokinetic and pharmacodynamic comparisons between Sermorelin and CJC-1295 No DAC in controlled human studies have not been published.

5. Evidence Status

Table 3 — CJC-1295 No DAC Evidence Hierarchy by Claim
Proposed Effect / Claim	Current Status	Evidence Level
GHRHR agonism mechanism (class-level)	Established through GHRH, Sermorelin, and tesamorelin research; Frohman & Jansson 1986	Moderate
Modified GRF(1-29) framework GHRHR activity	Demonstrated via CJC-1295 with DAC Phase 1 (Teichman 2006); DAC form only	Moderate
DPP-IV resistance via D-Ala² substitution	Established from enzymatic degradation studies; Frohman et al. 1989	Moderate
Improved plasma stability vs. Sermorelin	Expected from D-Ala² modification; formal human PK for No DAC form not published	Limited
GH release in humans (No DAC form specifically)	No formal published Phase 1 PK/PD study for CJC-1295 No DAC identified as of the review date	Limited
IGF-1 elevation (No DAC form)	Mechanistically expected from GHRHR agonism; not characterized in published controlled human trials	Limited
Clinical efficacy (any approved indication)	No regulatory approval in any jurisdiction; no Phase 3 trials published	Limited

What We Still Don’t Know

Formal human pharmacokinetics for the No DAC form: The plasma half-life estimate of approximately 30 minutes for CJC-1295 No DAC is widely referenced but derives from the expected benefit of DPP-IV protection rather than a published pharmacokinetic study in human subjects. The actual half-life, volume of distribution, metabolic clearance pathways, and active metabolite profile in human plasma have not been characterized in published peer-reviewed literature as of the review date.
Dose-response relationship in humans: The dose of CJC-1295 No DAC required to produce a defined GH pulse amplitude in humans, and the dose at which off-target or tolerance effects might emerge, have not been established in published controlled pharmacodynamic studies. Research extrapolations from the DAC form cannot be directly applied to the No DAC form due to their different pharmacokinetic profiles.
Direct comparison with Sermorelin: Whether Modified GRF(1-29) produces a meaningfully different GH response profile than native Sermorelin at equivalent active exposure levels — or whether the four modifications confer a clinically relevant pharmacodynamic advantage in addition to improved chemical stability — has not been established in published head-to-head studies.
Long-term safety of chronic GH pulse amplification: The implications of sustained GHRHR agonism over months to years — including effects on the endogenous GH axis, IGF-1 maintenance, oncologic considerations, and potential tachyphylaxis — have not been characterized in published prospective human studies for CJC-1295 No DAC or any related short-acting GHRH analogue outside of Sermorelin’s limited clinical history.
Combination data with GHSR-1a agonists: The mechanistic rationale for combining CJC-1295 No DAC with GHSR-1a agonists is well-supported by endocrinology literature, but specific combination protocols have not been evaluated in published randomized controlled human trials for any defined endpoint.

6. Limitations of Current Research

No Regulatory Approval and Absent Phase 3 Data CJC-1295 No DAC has not been approved by the FDA or any comparable regulatory authority for any indication. No Phase 3 clinical trial results for this compound have been published in peer-reviewed literature. Clinical efficacy and long-term safety in human subjects have therefore not been evaluated at the standard required for clinical use.

Published Clinical Data Primarily for the DAC Form The most directly relevant human pharmacology evidence for the CJC structural series — the Teichman et al. (2006) Phase 1 trial — evaluated CJC-1295 with DAC, not the No DAC form. These two compounds have substantially different pharmacokinetic profiles: the DAC form has a half-life of approximately 7–8 days; the No DAC form is estimated at approximately 30 minutes. The GH and IGF-1 profiles produced by these two forms differ accordingly, and findings from the DAC trial cannot be extrapolated to the No DAC form for dose estimation, dosing frequency, or expected pharmacodynamic magnitude.

Nomenclature Ambiguity Complicates Literature Interpretation The term “CJC-1295” is used inconsistently across research literature, commercial contexts, and online communities — sometimes referring to the albumin-binding DAC form, sometimes to the No DAC form (Modified GRF 1-29), and occasionally without specifying which compound is meant. This ambiguity can make it difficult to attribute specific pharmacological findings to the correct compound. References to CJC-1295 without explicit DAC specification should be interpreted with caution, and the compound name “Modified GRF 1-29” or “Mod GRF(1-29)” is more unambiguous when referring specifically to the No DAC form.

Half-Life Estimate Not Formally Confirmed in Human PK Studies The approximately 30-minute plasma half-life widely cited for CJC-1295 No DAC is an estimate based on the expected benefit of D-Ala² DPP-IV protection relative to native Sermorelin (approximately 2–3 minutes). A formal published pharmacokinetic study directly measuring plasma concentration–time profiles for CJC-1295 No DAC in human subjects has not been identified in the peer-reviewed literature as of the review date. The actual in vivo half-life in humans may differ from current estimates depending on additional proteolytic pathways and individual pharmacokinetic variation.

Long-Term Human Safety Data Unavailable No published long-term safety data from controlled human trials exist for CJC-1295 No DAC or the CJC series more broadly. The chronic implications of sustained GHRHR-mediated GH pulse amplification — including oncologic considerations related to elevated IGF-1, effects on the endogenous GH axis with prolonged use, and potential desensitization of GHRHR signaling — have not been characterized in published prospective human studies. No systematic pharmacovigilance data in a large treated population are available.

ConjuChem No Longer Appears to Have Active Development Programs ConjuChem Biotechnologies, the developer of the CJC series and the DAC technology platform, no longer appears to have active pharmaceutical development programs for CJC-1295 based on publicly available information. The absence of an active commercial sponsor pursuing regulatory development reduces the likelihood of future Phase 3 trials or regulatory submissions that might generate additional published human pharmacology or safety data for this compound series.

⚠ Research and Informational Use Only. All content on this page is for informational and educational purposes and is intended for qualified research professionals. Nothing on this page constitutes medical advice, diagnosis, or treatment guidance. CJC-1295 No DAC is supplied by Wholesale Peps as lyophilized powder for in vitro laboratory research only and is not approved by the FDA for human or veterinary use. Wholesale Peps is not affiliated with, endorsed by, or associated with ConjuChem Biotechnologies. Read full disclaimer →

References

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.” Journal of Clinical Endocrinology & Metabolism. 2006;91(3):799–805. doi:10.1210/jc.2005-1536
Frohman LA, Downs TR, Heimer EP, Felix AM. “Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma.” Journal of Clinical Investigation. 1989;83(5):1533–1540. doi:10.1172/JCI114050
Frohman LA, Jansson JO. “Growth hormone-releasing hormone.” Endocrine Reviews. 1986;7(3):223–253. doi:10.1210/edrv-7-3-223
Walker RF. “Sermorelin: a better approach to management of adult-onset growth hormone insufficiency?” Clinical Interventions in Aging. 2006;1(4):307–308. doi:10.2147/ciia.2006.1.4.307
Veldhuis JD, Bowers CY. “Human GH pulsatility: an ensemble property regulated by age and gender.” Journal of Endocrinological Investigation. 2003;26(9):799–813. doi:10.1007/BF03345234

CJC-1295 (No DAC)