CJC-1295 No DAC

Overview

CJC-1295 No DAC is a synthetic analogue of growth hormone-releasing hormone, built on the 29-residue active fragment of GHRH and carrying four amino acid substitutions that protect it from the enzymes that destroy the native hormone within minutes. It is studied as a research tool for stimulating pituitary growth hormone release on a short, pulse-like timescale.

It is closely related to, but pharmacologically quite different from, CJC-1295 with DAC. The two share the same peptide backbone and the same receptor. What separates them is duration — roughly half an hour against roughly a week — and that single difference changes the kind of signal each produces.

A note on the name

The naming here is genuinely confusing, and worth clearing up because it affects what you find when searching the literature.

The compound is widely sold and discussed as “CJC-1295 without DAC”, but strictly that is a contradiction. CJC-1295 is the albumin-binding conjugate; the Drug Affinity Complex is the defining feature of the molecule that received that code. Removing it does not give a variant of CJC-1295 — it gives the tetrasubstituted GHRH fragment that the DAC was attached to in the first place.

That underlying peptide is properly called modified GRF (1-29), usually shortened to Mod GRF 1-29, and sometimes written as tetrasubstituted GRF(1-29). Searching that name rather than “CJC-1295 no DAC” will surface a different and generally more technical body of material.

Chemical identity

• Also known as: Mod GRF 1-29, tetrasubstituted GRF(1-29)
• CAS number: 863288-34-0
• Molecular formula: C₁₅₂H₂₅₂N₄₄O₄₂
• Molecular weight: 3367.9 g/mol
• Classification: GHRH analogue, GHRH receptor agonist
• Length: 29 residues
• Appearance: White lyophilised powder

At 3,368 g/mol this is too large for a two-dimensional structure diagram to be legible — twenty-nine residues rendered at reading size is a tangle of overlapping bonds. The sequence and its four modifications are described below instead, which is the more useful representation for a peptide of this size.

The problem the modifications solve

Native GHRH is a 44-residue hypothalamic hormone, but its biological activity resides almost entirely in the first 29 residues — GHRH(1-29) is the shortest fragment that fully activates the receptor. That fragment alone, however, is close to useless as a research tool, because plasma destroys it in minutes.

The culprit is dipeptidyl peptidase-4 (DPP-4), which cleaves the peptide between residues 2 and 3, removing the N-terminal dipeptide and abolishing receptor activity. The reported plasma half-life of unmodified GHRH(1-29) is on the order of seven minutes. Any GHRH analogue intended to survive long enough to be studied has to solve that cleavage first.

The four substitutions

Mod GRF 1-29 differs from GHRH(1-29) at four positions, and each change addresses a specific liability:

• Position 2: alanine to D-alanine. The critical one. DPP-4 recognises L-amino acids at this position; substituting the D-enantiomer blocks cleavage without altering receptor binding. This alone extends the half-life several-fold.
• Position 8: asparagine to glutamine. Asparagine residues are prone to deamidation and backbone rearrangement, which degrades the peptide in storage as well as in solution. Glutamine is chemically similar but far more stable.
• Position 15: glycine to alanine. Glycine is conformationally flexible; alanine favours the helical structure the receptor binds, which is associated with increased potency.
• Position 27: methionine to leucine. Methionine oxidises readily — a shelf-life and handling liability rather than a plasma one. Leucine is similar in size and hydrophobicity but not oxidisable.

Two of these address plasma stability, and two address chemical stability in the vial. That is worth noting when handling the material: the compound is more robust in storage than unmodified GHRH would be, by design.

Mechanism of action

Mod GRF 1-29 binds the GHRH receptor on pituitary somatotroph cells, a G-protein coupled receptor that signals through adenylyl cyclase and cyclic AMP to trigger synthesis and release of growth hormone. Because it acts on the pituitary rather than supplying growth hormone directly, the output remains subject to the body’s own regulation — most importantly somatostatin, which opposes GHRH signalling and sets the trough between natural GH pulses.

That regulatory ceiling is the mechanistic reason this class is studied at all. A GHRH analogue amplifies an existing signal within the constraints of the axis, rather than overriding it.

Pulsatile signalling and why it is studied this way

Growth hormone is not secreted continuously. It is released in discrete bursts, largely during slow-wave sleep, with near-undetectable troughs between them. That pattern is not incidental: receptor responsiveness, downstream signalling and IGF-1 production all respond differently to a pulsed signal than to a flat elevated one.

With a half-life measured in tens of minutes rather than days, Mod GRF 1-29 produces a discrete pulse of GH release that decays — approximating the natural pattern rather than replacing it with continuous stimulation. Research designs interested in physiological patterning generally use the non-DAC form for exactly this reason, and often pair it with a growth hormone secretagogue acting through the separate ghrelin-receptor pathway, on the reasoning that two complementary signals produce a larger pulse than either alone.

How it compares with the DAC version

The practical differences follow entirely from duration:

• Half-life: roughly 30 minutes, against roughly 6–8 days for the DAC conjugate.
• Signal shape: a discrete pulse that decays, against sustained elevation.
• Study cadence: frequent administration to produce repeated pulses, against infrequent administration producing continuous exposure.
• What each is used to study: physiological pulse patterning, against sustained axis stimulation.

Neither is a better version of the other — they answer different questions. The DAC version is covered separately.

Handling, reconstitution and storage

• Lyophilised storage: sealed, refrigerated, protected from light. Freeze for long-term storage.
• Reconstitution: add diluent slowly against the vial wall and let the powder dissolve undisturbed. Do not shake — foaming denatures peptides.
• After reconstitution: refrigerate, protect from light, minimise freeze–thaw cycles. The Met-to-Leu substitution removes the most oxidation-prone residue, which makes this peptide somewhat more forgiving in solution than the unmodified fragment, but it is still a 29-residue peptide and should be treated as one.
• Concentration: our peptide reconstitution calculator converts vial quantity, diluent volume and syringe size into concentration per unit.

Purity and analytical verification

A 29-residue synthesis has twenty-nine opportunities for an incomplete coupling, and the resulting deletion sequences are chemically similar to the target — similar enough to co-elute on a poorly resolved chromatogram.

There is a further verification question specific to this compound. Three of its four modifications are conservative substitutions between similar residues, and one is a change of stereochemistry rather than of atom count. The D-alanine at position 2 does not change the molecular formula at all — a batch synthesised with L-alanine would be indistinguishable by mass spectrometry while being the DPP-4-susceptible peptide the modifications exist to avoid. Mass confirmation alone cannot detect that error.

What can is sequencing, or a chiral analysis, neither of which appears on a typical certificate of analysis. In practice HPLC purity plus mass confirmation is what is available; it is worth understanding what that does and does not establish.

We publish third-party certificates of analysis by batch.

References

• Frohman LA, Downs TR, Williams TC, et al. Rapid enzymatic degradation of growth hormone-releasing hormone by plasma in vitro and in vivo to a biologically inactive product cleaved at the NH₂ terminus. Journal of Clinical Investigation, 1986. PMID 3093533
• 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. Endocrinology, 2005. PMID 15817669

Summary

CJC-1295 No DAC — more accurately Mod GRF 1-29 — is a tetrasubstituted analogue of GHRH(1-29), CAS 863288-34-0, molecular formula C₁₅₂H₂₅₂N₄₄O₄₂, molecular weight 3,367.9 g/mol. Four substitutions protect it from DPP-4 cleavage, deamidation and oxidation, extending its plasma half-life from roughly seven minutes to roughly thirty. It agonises the GHRH receptor on pituitary somatotrophs, producing a discrete pulse of growth hormone release that decays — the property that distinguishes it from the albumin-binding DAC conjugate, which produces sustained exposure instead.

For laboratory research use only. Not for human consumption. This material is not a drug, food, or cosmetic and may not be sold or used for any purpose other than in vitro or non-human laboratory research.