CJC-1295 With DAC

Overview

CJC-1295 with DAC is a growth hormone-releasing hormone analogue engineered for exceptional duration. It combines a modified 29-residue GHRH fragment with a Drug Affinity Complex — a chemical group that binds covalently to circulating albumin, converting a peptide with a half-life of minutes into one measured in days.

It is the compound to which the CJC-1295 designation properly belongs. The related CJC-1295 No DAC is the same peptide backbone without that conjugation, and behaves quite differently as a result.

Chemical identity

• CAS number: 446262-90-4
• Molecular formula: C₁₆₅H₂₆₉N₄₇O₄₆
• Molecular weight: 3647.9 g/mol
• Classification: Long-acting GHRH analogue, albumin-binding conjugate
• Length: 30 residues plus the DAC linker
• Appearance: White lyophilised powder

The 280 g/mol difference between this compound and the non-DAC form is the conjugation chemistry: an additional lysine residue at position 30 and the reactive linker attached to it. Everything else about the peptide is the same.

At 3,648 g/mol the molecule is well past the point where a two-dimensional depiction remains readable, so its architecture is described rather than drawn.

What the Drug Affinity Complex is

The DAC is a maleimide group attached through a short linker to the lysine added at position 30. Maleimides react rapidly and selectively with free thiols — specifically, with cysteine side chains — forming a stable covalent bond.

Serum albumin, the most abundant protein in plasma, carries exactly one free cysteine available for this reaction: Cys34. The result is that within a short time of entering circulation, the peptide finds albumin and attaches to it permanently, becoming a peptide–protein conjugate rather than a free peptide.

That changes its fate entirely. A 3.6 kDa peptide is small enough to be filtered by the kidney within minutes; a 70 kDa albumin conjugate is not. Albumin also has its own long circulatory lifetime and recycling machinery, and the bound peptide inherits it. Reported half-lives for the conjugate are in the range of six to eight days, against roughly thirty minutes for the same peptide without the DAC.

The elegance of the approach is that conjugation happens in vivo, after administration. The compound is handled and stored as an ordinary lyophilised peptide; the albumin binding occurs only on contact with plasma.

Mechanism of action

Once bound, the conjugate still acts at the GHRH receptor on pituitary somatotrophs, signalling through cyclic AMP to trigger growth hormone synthesis and release. The receptor pharmacology is that of the underlying peptide; what the DAC changes is not what the molecule does but how long it remains available to do it.

Because output is still mediated through the pituitary, it remains subject to somatostatin opposition and to negative feedback from IGF-1 — the axis retains its own regulation rather than being bypassed.

Sustained versus pulsatile exposure

This is the substantive difference between the two forms, and the reason the choice between them matters in a study design.

Growth hormone is normally secreted in discrete bursts with near-undetectable troughs between them. A compound with a multi-day half-life does not reproduce that pattern; it produces continuous receptor stimulation, and the resulting profile is a sustained elevation of GH and IGF-1 rather than a series of peaks.

Whether that matters is an interesting question rather than a settled one, and it is where the published research on this compound is most worth reading. Work by Ionescu and Frohman examined precisely this and reported that pulsatile GH secretion persisted during continuous stimulation by CJC-1295 — that is, the underlying pulse generator continued to operate on top of the elevated baseline, rather than being flattened by it. That finding is more nuanced than the simple “continuous versus pulsatile” framing usually applied to these two compounds, and anyone choosing between them should read it directly.

Research record

CJC-1295 has a more substantial published record than most compounds in this catalogue, including human pharmacokinetic work.

• Duration and exposure. Teichman and colleagues reported that single administrations produced sustained elevation of growth hormone and IGF-1 across multiple days, establishing the extended-duration profile that the DAC was designed to achieve.
• Pulse dynamics. Ionescu and Frohman examined whether continuous stimulation abolishes GH pulsatility, and reported that it does not.
• Conjugation chemistry. Earlier work by Jetté and colleagues characterised the albumin bioconjugate approach and identified CJC-1295 as the long-acting analogue arising from it.

How it compares with the non-DAC version

• Half-life: roughly 6–8 days, against roughly 30 minutes.
• Signal shape: sustained elevation with pulses superimposed, against discrete decaying pulses.
• Study cadence: infrequent administration, against frequent.
• Mass: 3,647.9 against 3,367.9 g/mol — the difference is the added residue and linker.
• What each is used to study: sustained axis stimulation, against physiological pulse patterning.

Full detail on the shorter-acting form is on the CJC-1295 No DAC page.

Handling, reconstitution and storage

Handled as an ordinary lyophilised peptide — the albumin conjugation happens only on contact with plasma and has no bearing on storage. One consideration is specific to this compound:

• Lyophilised storage: sealed, refrigerated, protected from light; freeze for long-term storage.
• Reconstitution: add diluent slowly down the vial wall, allow to dissolve undisturbed, do not shake.
• Thiol contamination matters here. The maleimide group is reactive by design and will couple to any available free thiol, not only albumin’s. Diluents or containers carrying thiol contamination can consume the linker before use. Standard bacteriostatic water is not a concern; reducing agents such as DTT or beta-mercaptoethanol would be.
• After reconstitution: refrigerate, protect from light, minimise freeze–thaw cycles.
• Concentration: our peptide reconstitution calculator handles the arithmetic.

Purity and analytical verification

Two questions matter for this compound, and only one is answered by a routine certificate.

Peptide purity is the standard question: HPLC quantifies how much of the material is the intended sequence rather than deletion variants from incomplete coupling.

Linker integrity is the one specific to a DAC conjugate. The maleimide is the functional element — without an intact one the compound is simply the non-DAC peptide with an extra lysine, and would behave like a thirty-minute peptide rather than a multi-day one. Because maleimides hydrolyse over time in aqueous conditions, this is a real degradation route rather than a theoretical one. Mass spectrometry addresses it: the measured mass distinguishes intact conjugate from hydrolysed linker, which differ by the mass of water.

A certificate showing HPLC purity alone establishes that the peptide is clean, not that the linker is intact. For this compound, ask for the mass.

We publish third-party certificates of analysis by batch.

References

• Teichman SL, Ball SD, Ferris JA, et al. 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. PMID 16352683
• Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. Journal of Clinical Endocrinology & Metabolism, 2006. PMID 17018654
• 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 with DAC is a long-acting GHRH analogue, CAS 446262-90-4, molecular formula C₁₆₅H₂₆₉N₄₇O₄₆, molecular weight 3,647.9 g/mol. A maleimide linker on a lysine at position 30 binds covalently to Cys34 of serum albumin after administration, extending the plasma half-life from roughly thirty minutes to roughly six to eight days. Receptor pharmacology is unchanged from the underlying peptide; what changes is duration, producing sustained rather than pulsed stimulation of the growth hormone axis — though published work reports that endogenous pulsatility persists on top of that elevated baseline.

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.