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

CJC-1295 no DAC, more precisely named Modified GRF (1-29) or tetrasubstituted hGRF(1-29)-NH2, is the 29-residue growth-hormone-releasing hormone fragment with four amino-acid substitutions: D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27. It is the peptide core of CJC-1295 without the C-terminal lysine-maleimide Drug Affinity Complex that gives the full CJC-1295 its albumin binding and multi-day half-life [4]. The name “CJC-1295 no DAC” is a marketplace convention rather than a name used in the primary literature, where the compound appears as an intermediate in the structure–activity work that led to CJC-1295 and to other stabilised GRF analogs.

Why the four substitutions exist

Each change addresses a specific weakness of native GHRH identified in the 1980s and 1990s stability literature.

• D-Ala2 — Frohman et al. showed in 1986 that plasma dipeptidyl peptidase IV removes the N-terminal Tyr-Ala dipeptide within minutes, leaving an inactive GHRH(3-44) product [2]. A D-amino acid at position 2 is not recognised by the enzyme, and this single change is the largest contributor to plasma stability.
• Gln8 replaces asparagine, which in the native sequence deamidates and isomerises in solution and in tissue, generating iso-aspartyl species with reduced activity. Glutamine is far less susceptible.
• Ala15 replaces glycine. Alanine has a high helix propensity, and GHRH must adopt an amphipathic α-helix to bind its receptor; the substitution is reported to increase receptor affinity and potency in systematic structure–activity studies [1].
• Leu27 replaces methionine, whose side chain oxidises to the sulfoxide during synthesis, storage and in vivo, again lowering potency. Leucine is isosteric and non-oxidisable.

Campbell and colleagues (1994) described how combining substitutions of this kind, drawn from rodent and human GRF sequences, produced analogs with markedly enhanced plasma stability and potency relative to hGRF(1-29) [3]. Cervini et al. (1998) published the systematic single-residue scan of hGHRH(1-29)-NH2 that underpins most of these choices [1]. In Jetté et al. (2005) the tetrasubstituted sequence is the starting scaffold onto which the maleimide linker is added; the paper reports that the substitutions confer resistance to DPP-IV in vitro and retained GH-releasing activity in rat pituitary cells [4].

Pharmacological profile

Without the albumin linker, the compound is cleared like other small peptides. Its half-life is not reported in a dedicated human study, but is expected to be on the order of tens of minutes rather than the 5.8–8.1 days measured for the DAC conjugate [4]. The practical consequence in a research design is a discrete, short GH pulse that ends when the peptide is cleared, in contrast to the days of elevated trough GH and IGF-1 produced by CJC-1295 with DAC. This is the reason the no-DAC form exists as a separate product: it lets an investigator study a stabilised GHRH-receptor agonist while retaining a pulsatile, on–off exposure pattern. Because GHRH-receptor and ghrelin-receptor (GHS-R1a) agonists act synergistically on somatotrophs, the short-acting form is also the one most often paired with GHRPs such as ipamorelin in the endocrine literature on combined stimulation.

Identification and regulatory position

Doping-control laboratories have characterised both the DAC and no-DAC forms by mass spectrometry, and Henninge et al. (2010) reported the identification of CJC-1295 in an unlabelled seized preparation, establishing analytical reference data now used to distinguish the two [5]. FDA treats Modified GRF (1-29) as a CJC-1295-related substance: its December 2024 Pharmacy Compounding Advisory Committee briefing covered CJC-1295 free base and acetate alongside the DAC salts and proposed that none be added to the section 503A bulks list [6].

What the research does not establish

There is no published clinical trial of Modified GRF (1-29) as a stand-alone compound. The human pharmacokinetic and GH/IGF-1 data associated with the name CJC-1295 come entirely from the DAC conjugate and do not transfer to the no-DAC peptide, whose exposure profile is fundamentally different. The stability and potency claims for the four substitutions derive from in-vitro enzyme assays, rat pituitary cell cultures and rodent studies [1][3][4]; the relative potency figures vary with the assay and species used. Nothing in the literature establishes body-composition, performance or ageing effects, and FDA's 2024 review proposed against listing the substance for compounding on the basis of the evidence available [6]. This material is supplied strictly for in-vitro laboratory research.

Format. Lyophilized powder in a sealed glass vial. The peptide is supplied as the acetate salt; stated mass refers to the peptide.

Reconstitution. Reconstitute with bacteriostatic water, directing the stream against the glass wall rather than onto the powder cake, then swirl gently until dissolved — do not shake. Our reconstitution calculator converts vial mass and diluent volume into concentration and U-100 syringe units.

Storage. Lyophilized vials are typically stored at −20 °C and protected from light. The Gln8 and Leu27 substitutions remove the deamidation and oxidation liabilities of native GHRH, so the modified sequence is more forgiving in solution than sermorelin, but reconstituted solutions should still be refrigerated at 2–8 °C and aliquoted before freezing to avoid repeated freeze-thaw cycles.

Handling. Standard laboratory practice applies: appropriate PPE, aseptic technique when reconstituting, and disposal in line with your institution's procedures. For in-vitro laboratory research only — not for human or veterinary use.