CJC-1295 DAC vs No-DAC

CJC-1295 With DAC vs Without DAC: A Naming Problem That Changes Experimental Design

Walk the US research supply market and you will find two products sold under one name. “CJC-1295 (with DAC)” and “CJC-1295 (no DAC)” are listed side by side, priced differently, and described as though the difference is a formulation detail — a longer-acting version and a shorter-acting version of the same molecule.

That framing does not survive contact with the primary literature. The two materials are different compounds with different half-lives, different plasma-residence behavior, and different consequences for how a growth hormone axis experiment is designed. A research team that treats them as interchangeable is not choosing a duration setting. It is running a different experiment than it thinks it is running.

This article covers what the published work actually established, what the distinction means for study design, and how to confirm from a Certificate of Analysis which of the two is in the vial.

The name belongs to the conjugate

The compound was characterized by Jetté and colleagues at ConjuChem in Endocrinology in 2005 (PMID 15817669). The group synthesized three maleimido derivatives of human growth hormone-releasing factor (hGRF) 1-29 and conjugated them to human serum albumin. The paper’s own definition is explicit: CJC-1295 is a tetrasubstituted form of hGRF(1-29) carrying an added N-epsilon-3-maleimidopropionamide derivative of lysine at the C-terminus.

That maleimide group is the Drug Affinity Complex. It is not an accessory bolted onto CJC-1295 — it is the part of the molecule the name was assigned to. Strip it off and what remains is the tetrasubstituted hGRF(1-29) backbone, which the field more accurately calls modified GRF(1-29). The market label “CJC-1295 without DAC” describes a molecule that pre-dates the CJC-1295 designation and is chemically distinct from it.

This matters because the two halves of the molecule do different jobs, and only one of them is shared.

What the four substitutions do

Native GHRH is cleared from plasma with brutal efficiency. Frohman and co-workers, working in The Journal of Clinical Investigation in 1989 (PMID 2565342), identified the primary cleavage as a single-step dipeptidylpeptidase IV cut at the 2-3 amino acid bond. Native GRH(1-44)-NH2, GRH(1-40)-OH, and the shortened GRH(1-32)-NH2 and GRH(1-29)-NH2 fragments were all rapidly cleaved at that site. Critically, the same paper showed that D-amino acid substitution at position 1 or 2 prevented the hydrolysis. Kubiak and colleagues in Drug Metabolism and Disposition the same year (PMID 2571478) reported the corresponding plasma half-lives for a bovine GRF analog — 8.4 minutes in porcine plasma, 22.1 minutes in bovine plasma — and showed that a competitive DPP-IV inhibitor extended it to 83.3 minutes.

The tetrasubstitution in the hGRF(1-29) backbone is the structural answer to that problem. It buys resistance to enzymatic degradation. In the Jetté work, all three albumin conjugates showed enhanced in vitro stability against dipeptidylpeptidase-IV and remained bioactive in a GH secretion assay in cultured rat anterior pituitary cells.

But resistance to a protease is not the same thing as long residence in circulation. Substitution changes minutes into somewhat more minutes. It does not change minutes into days.

What the DAC adds

The albumin conjugate is what changes the timescale, and the effect size in the original rat work is specific. When the maleimido derivatives were administered subcutaneously to normal male Sprague-Dawley rats, the best compound — CJC-1295 — produced a four-fold increase in GH area under the curve over a two-hour period compared with unmodified hGRF(1-29), and was still present in plasma beyond 72 hours. Western blot analysis of plasma from an injected rat showed CJC-1295 immunoreactivity on the band corresponding to serum albumin, appearing at 15 minutes and still in circulation past 24 hours.

The mechanism is covalent capture. The maleimide reacts with the free thiol on Cys34 of serum albumin in vivo, and the peptide then travels on the albumin pool rather than being cleared as a free peptide.

In published human pharmacology, Teichman and colleagues reported in the Journal of Clinical Endocrinology and Metabolism in 2006 (PMID 16352683) that the estimated half-life of CJC-1295 was 5.8 to 8.1 days, with plasma GH elevated for six days or more after a single subcutaneous administration and IGF-I elevated for nine to eleven days. That is published clinical pharmacology literature describing a pharmaceutical-grade investigational material, cited here to establish the pharmacokinetic contrast. It is not use guidance and does not describe research-grade material.

The gap between the two compounds is therefore roughly three orders of magnitude in duration. That is not a formulation variant.

The design consequence most comparisons miss

The interesting finding is not that the conjugate lasts longer. It is what the sustained signal does to the shape of GH output.

Ionescu and Frohman, in JCEM in 2006 (PMID 17018654), sampled blood every 20 minutes across a 12-hour overnight window before and one week after a single administration of CJC-1295 in healthy young men. Pulsatility was preserved. The frequency and magnitude of GH secretory pulses were unaltered. What changed was the floor: basal trough GH levels rose 7.5-fold (P < 0.0001), driving a 46% increase in mean GH (P < 0.01) and a 45% increase in IGF-I (P < 0.001). The IGF-I increases did not correlate with any parameter of GH secretion measured.

Read that carefully, because it inverts the intuitive expectation. Continuous GHRH-receptor stimulation did not amplify the peaks. It raised the baseline between them.

For an experimental model, that is the whole distinction. A study asking about pulse amplitude, pulse-dependent signaling, or the somatostatin-driven inter-pulse trough is measuring something the DAC compound systematically alters — the baseline is no longer the baseline. A study asking about sustained tonic GHRH-receptor occupancy is measuring something a minutes-scale analog cannot produce at all, no matter the administration interval.

Administration interval still matters even at an eight-day half-life. Alba and colleagues, in American Journal of Physiology — Endocrinology and Metabolism in 2006 (PMID 16822960), gave 2 µg of CJC-1295 to GHRH-knockout mice at 24-, 48-, and 72-hour intervals for five weeks. The once-daily group reached normal body weight and length. The 48- and 72-hour groups exceeded placebo but did not fully normalize. The same paper reported increased total pituitary RNA and GH mRNA with immunohistochemical confirmation of somatotroph proliferation — a tissue-level change on the pituitary itself, which is a different dependent variable from circulating hormone and worth designing for.

Why the blend on this site uses the no-DAC form

The CJC-1295/Ipamorelin Blend 10MG stocked here contains 5 mg of CJC-1295 (No DAC) — modified GRF(1-29) — and 5 mg of ipamorelin. That pairing is a pharmacological decision, not a cost one.

The two compounds act through separate receptors. Cheng and colleagues at Merck established this in Endocrinology in 1989 (PMID 2541999): GHRP-6 stimulated GH release from rat primary pituitary cells with half-maximal stimulation at 7 × 10⁻⁹ M, and that release was not blocked by the GRF antagonist [N-Ac-Tyr¹,D-Arg²]GRF-(1-29)-NH2. GHRP-6 had no effect on intracellular cAMP, whereas GRF raised it three-fold. Given together at maximal concentrations, the two produced synergistic GH release and potentiated the cAMP rise. Desensitization was receptor-arm specific and fully reversible within an hour of peptide removal. Ipamorelin sits on the GHRP arm of that system: Raun and colleagues characterized it in the European Journal of Endocrinology in 1998 (PMID 9849822) with an EC₅₀ of 1.3 ± 0.4 nmol/l and Emax of 85 ± 5% in primary rat pituitary cells, and — the reason it is used as a tool compound at all — no significant ACTH or cortisol elevation in swine at doses more than 200-fold above the GH ED₅₀, where GHRP-6 and GHRP-2 both raised them.

Synergy of that kind requires the two signals to arrive at the somatotroph together. A short-acting GHRH-receptor agonist can be co-timed with a minutes-scale GHRP. An albumin-bound analog with a multi-day residence cannot be co-timed with anything — by design, it is always present. Combining a DAC compound with a GHRP does not produce the co-stimulation Cheng described; it produces a GHRP administered against a permanently raised GHRH-receptor baseline, which is a different model entirely.

If a study is built on the two-receptor synergy, the no-DAC form is the correct tool. If it is built on sustained tonic stimulation, the no-DAC form cannot deliver it and the blend is the wrong material.

Confirming which one is in the vial

The distinction is analytically visible, which means it does not have to be taken on trust. The maleimidopropionamide-lysine addition is a real mass difference, so mass spectrometric identity data on a batch Certificate of Analysis separates the two unambiguously. Observed mass against theoretical mass is the check. A COA that reports a purity percentage but no identity mass does not distinguish a DAC compound from a no-DAC compound, and neither does the label.

Two further points are worth checking on any US-sourced material of this class. CAS numbers are inconsistently applied across the two forms by suppliers, so a CAS number alone is not confirmation. And published pharmacokinetic work on the DAC conjugate is routinely cited on product pages for the no-DAC compound, which is a citation error rather than a data point — the Teichman and Ionescu results above describe the albumin conjugate and do not transfer.

Maple Research Labs ships this material domestically from our Santa Barbara, California facility, same-day on orders placed before cutoff, with a batch-specific COA and third-party HPLC verification on every lot. Domestic fulfillment matters more than convenience here: material that clears customs over an unpredictable window has an unpredictable thermal history, and the lyophilized state a COA describes at release is not what arrives if the material spent a week in transit.

Summary

• CJC-1295 as defined in the primary literature includes the DAC. The “no-DAC” product is modified GRF(1-29), a different compound.
• The tetrasubstitution confers DPP-IV resistance. The albumin conjugate confers multi-day plasma residence. These are separate structural features doing separate jobs.
• Sustained GHRH-receptor stimulation raised trough GH 7.5-fold without changing pulse frequency or amplitude. Baseline, not peak, is what moves.
• The two forms suit different questions. Co-stimulation designs need the short-acting form; tonic-stimulation designs need the conjugate.
• Mass spectrometric identity on a batch COA is the way to confirm which material is in hand.

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Compliance notice. All compounds referenced on this page are supplied for laboratory research use only. All findings described above derive from in vitro systems and animal models, or from published clinical pharmacology literature conducted on pharmaceutical-grade investigational material, which research-grade compounds are not. Nothing on this page is guidance for administration to people. These materials are not for human use, not for veterinary use, and not for diagnostic use.

References

1. 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;146(7):3052-8. PMID 15817669.
2. Frohman LA, Downs TR, Heimer EP, Felix AM. Dipeptidylpeptidase IV and trypsin-like enzymatic degradation of human growth hormone-releasing hormone in plasma. J Clin Invest. 1989;83(5):1533-40. PMID 2565342.
3. Kubiak TM, Kelly CR, Krabill LF. In vitro metabolic degradation of a bovine growth hormone-releasing factor analog in bovine and porcine plasma; correlation with plasma dipeptidylpeptidase activity. Drug Metab Dispos. 1989;17(4):393-7. PMID 2571478.
4. Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab. 2006;91(3):799-805. PMID 16352683.
5. Ionescu M, Frohman LA. Pulsatile secretion of growth hormone persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-7. PMID 17018654.
6. Alba M, Fintini D, Sagazio A, et al. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone analog, normalizes growth in the GHRH knockout mouse. Am J Physiol Endocrinol Metab. 2006;291(6):E1290-4. PMID 16822960.
7. Cheng K, Chan WW, Barreto A Jr, Convey EM, Smith RG. The synergistic effects of His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 on growth hormone-releasing factor-stimulated GH release and intracellular cAMP accumulation in rat primary pituitary cell culture. Endocrinology. 1989;124(6):2791-8. PMID 2541999.
8. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998;139(5):552-61. PMID 9849822.
9. Bowers CY, Sartor AO, Reynolds GA, Badger TM. On the actions of the growth hormone-releasing hexapeptide, GHRP. Endocrinology. 1991;128(4):2027-35. PMID 2004615.