"CJC-1295" is one name attached to two related but pharmacologically distinct molecules, and confusion between them is one of the most common mix-ups in the research-peptide market. Both start from the same engineered fragment of growth hormone-releasing hormone (GHRH). One — properly called CJC-1295 with DAC, or DAC:GRF — has a Drug Affinity Complex (DAC) attached that binds covalently to circulating albumin, stretching its duration of action to multiple days. The other — sold as "CJC-1295 no DAC" but referred to in the published literature as modified GRF(1-29) or tetrasubstituted GRF(1-29) — lacks that attachment and clears far faster. This page sets the two side by side on identity, mechanism, and evidence, without ranking one above the other. For full background on the shared chemistry, mechanism of action, and the compound's discontinued clinical history, see the dedicated article on CJC-1295.
Side-by-Side Overview
| CJC-1295 with DAC (DAC:GRF) | CJC-1295 no DAC (modified GRF(1-29)) | |
|---|---|---|
| Molecule identity | Tetrasubstituted GRF(1-29) with a maleimide-bearing DAC linker attached at the C-terminus via an added lysine residue [2] | The same tetrasubstituted GRF(1-29) backbone, without the DAC linker [2] |
| Naming note | The name the 2005 identification paper actually assigned to the DAC-bound bioconjugate [2] | A market name; the peptide's own published designation is "modified GRF(1-29)," not "CJC-1295" [2] |
| Half-life / mechanism | Multi-day apparent half-life — the DAC linker covalently binds serum albumin's Cys34 thiol, shielding the peptide from peptidase degradation and renal filtration [2][4] | Modified backbone without an albumin anchor; human half-life is not established by the cited studies [1][2] |
| Published human data | Two randomized, placebo-controlled ascending-dose trials in healthy adults (28 and 49 days), plus a dedicated pulsatility study [3][4] | None identified in the peer-reviewed record under either name [2] |
| GH/IGF-1 response (published) | Single dose: GH up 2-10x (≥6 days), IGF-1 up 1.5-3x (9-11 days); repeated dosing: IGF-1 elevation sustained to 28 days [4] | Not established by any published human trial; effects are extrapolated from backbone chemistry and from the DAC form's data, not directly measured [2] |
| Development history/status | Advanced to a Phase II lipodystrophy trial, halted in July 2006 after a participant death; program never resumed [5] | Never entered the clinical development pipeline under its own name; characterized only at the chemistry/in vitro/receptor-binding stage [2] |
The Shared Backbone
Both molecules start from the same starting material: GRF(1-29), the first 29 residues of native GHRH, which retain full biological activity but are degraded within minutes in circulation — chiefly by the enzyme dipeptidyl peptidase-4 (DPP-4) [1]. Researchers at ConjuChem Biotechnologies introduced four amino acid substitutions into this backbone in the work that first identified CJC-1295: D-alanine at position 2 (blocking the primary DPP-4 cleavage site), glutamine at position 8 (preventing deamidation), alanine at position 15 (preserving receptor bioactivity), and leucine at position 27 (preventing oxidation of the native methionine) [2]. This tetrasubstituted GRF(1-29) is the common ancestor of both products sold under the CJC-1295 name — it is also, on its own, the molecule the no-DAC product is supposed to be.
What DAC Actually Does
The second, separate step in the 2005 work was attaching a maleimide-bearing linker — the Drug Affinity Complex — to the C-terminus of the modified peptide via an added lysine residue. The maleimide group reacts with the single free cysteine thiol (Cys34) on human serum albumin, forming a permanent covalent thioether bond [2]. Once attached, the peptide is no longer a free small molecule cleared on its own terms; it is physically riding on albumin, a protein with a multi-day circulating lifespan, shielded from both peptidase attack and rapid kidney filtration. This is the entire mechanistic basis for the half-life gap between the two forms: the DAC-bound molecule tracks closer to albumin's own residence time, while the no-DAC form — despite its own DPP-4-resistance substitutions — lacks that albumin anchor; its human half-life is not measured in these studies [1][2][4].
Published Human Data: One Form, Not the Other
This is the sharpest asymmetry between the two products. The only published, controlled human data for anything called CJC-1295 come from two randomized, placebo-controlled, double-blind ascending-dose trials in healthy adults, lasting 28 and 49 days, reported together by Teichman and colleagues in 2006 [4]. In that work, a single injection of the DAC-bound molecule raised mean plasma GH concentrations 2- to 10-fold for six days or longer, and mean plasma IGF-1 concentrations 1.5- to 3-fold for nine to eleven days; with repeated administration, IGF-1 elevation was sustained through 28 days [4]. No comparable trial — no published human pharmacokinetic or pharmacodynamic study of any kind — exists for the no-DAC/modified GRF(1-29) form under either name. The no-DAC form's published evidence base is limited to the 2005 identification paper's in vitro protease-resistance and pituitary-cell bioactivity work [2]. Any claim about how the no-DAC form behaves in humans is an inference from its chemistry and from the DAC form's results, not a direct finding.
The Pulsatility Question
A separate, dedicated study examined whether the DAC-bound molecule's continuous receptor engagement collapses the body's normal pulsatile GH secretion into a flat, sustained elevation — sometimes described informally as GH "bleed." Healthy men received a single subcutaneous dose of the DAC form, with overnight 12-hour GH sampling performed before dosing and again roughly a week later. Despite a full week of continuous receptor engagement, GH secretion remained pulsatile: pulse frequency and magnitude were unchanged, while basal (trough) GH increased [3]. That finding is specific to the DAC-bound molecule under the sampling conditions tested; no published study has examined whether the shorter-acting no-DAC form, which does not sustain continuous receptor engagement in the same way, raises a comparable question at all. Short-acting GHRH analogs as a class are generally understood to track closer to a single, pulse-like secretory event tied to the injection itself, but that framing is drawn from the pharmacokinetics rather than from a no-DAC-specific pulsatility trial [1][2].
The 2006 Discontinuation
The DAC-bound molecule's most advanced clinical program was a multicenter, randomized, placebo-controlled Phase II trial in roughly 192 participants with HIV-associated lipodystrophy. It was halted in July 2006 after a participant died of an acute myocardial infarction approximately two hours after an eleventh injection of study drug. The attending physician's assessment at the time attributed the death most likely to pre-existing coronary artery disease with plaque rupture, judged unrelated to the study drug — but ConjuChem terminated the trial as a precaution [5]. The program was never resumed, no controlled efficacy results from it were ever published, and no form of CJC-1295 has advanced past small early-phase studies in healthy volunteers since. This history belongs to the DAC-bound molecule specifically, since it was the only form to reach that stage of development; the no-DAC form never entered a comparable clinical pipeline under its own name.
Why the Naming Causes Confusion
"CJC-1295" was the name the original 2005 paper gave to the DAC-bound bioconjugate — the molecule with the linker attached [2]. "CJC-1295 no DAC" is a research-market label describing the same backbone minus that linker, but it borrows the parent name for a molecule the literature itself calls something else entirely: modified GRF(1-29). Because product labeling in the research-peptide market is not drawn from the peptide's original characterization, researchers evaluating vendor-sourced material should not assume that a product name reliably identifies which molecule, or which body of literature, actually applies to what is in the vial.
References
- Frohman LA, Jansson JO. Growth hormone-releasing hormone. Endocr Rev. 1986;7(3):223-253. doi:10.1210/edrv-7-3-223 — PMID: 2874984
- 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):3052-3058. doi:10.1210/en.2004-1286 — PMID: 15817669
- Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. J Clin Endocrinol Metab. 2006;91(12):4792-4797. doi:10.1210/jc.2006-1702 — PMID: 17018654
- 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. J Clin Endocrinol Metab. 2006;91(3):799-805. doi:10.1210/jc.2005-1536 — PMID: 16352683
- Lipodystrophy study halted after patient death. aidsmap, July 2006. Available at: aidsmap.com
This article is an educational summary of published research. It is not medical advice, and it does not describe, endorse, or recommend any use of CJC-1295 in humans. Neither CJC-1295 with DAC nor CJC-1295 no DAC (modified GRF(1-29)) is an approved drug. Products referenced on this site are sold for laboratory research use only.