CJC-1295 (DAC, No DAC, and Modified GRF 1-29): A Research Overview

Three molecules, one confusing name. CJC-1295 with DAC, CJC-1295 without DAC, and Modified GRF (1-29) all get called “CJC-1295” at some point, and researchers mix them up all the time. They do share a backbone, the 29 amino acid fragment of growth hormone releasing hormone (the hypothalamic peptide, GHRH). But drop them into plasma and they act nothing alike. What follows is what the primary papers actually measured, and we linked every one so you can argue with us.

What the molecule actually is

Start with the parent. GRF(1-29) is the first 29 residues of GHRH, and it turns out that short stretch carries the whole thing’s activity at the receptor [4]. The receptor lives on somatotroph cells in the anterior pituitary. It’s a class B G protein coupled receptor, so when GHRH binds, the cell cranks up adenylyl cyclase, cyclic AMP climbs, and out comes growth hormone [5]. All three “CJC” variants hit that same receptor. The only thing separating them is how long they survive before enzymes get to them.

Why native GRF(1-29) dies so fast

Blame the N-terminus. DPP-IV clips the first two residues clean off, and both the gut and plasma versions of that enzyme do it quickly [1]. Modified GRF (1-29), sometimes written mod GRF, swaps in substitutions around that cut site to slow the enzyme. It helps a little. It doesn’t change the big picture: the peptide still clears in minutes, not days.

The DAC trick: borrowing albumin’s half-life

Now the clever bit. DAC stands for Drug Affinity Complex. Jetté and his group built three maleimido versions of hGRF(1-29) and let them react with the free thiol on Cys34 of serum albumin [2]. Albumin sticks around for weeks, so bolt the peptide to it and the peptide hitches a ride. All three conjugates shrugged off DPP-IV and still triggered growth hormone release in cultured rat pituitary cells. The winner, which they named CJC-1295, produced a 4 fold bigger growth hormone area under the curve over 2 hours than plain hGRF(1-29), and a Western blot caught it sitting on the albumin band past 24 hours. That one modification is the entire “with DAC” versus “without DAC” story.

What the human data showed

Teichman and colleagues ran two placebo-controlled trials in healthy adults, ages 21 to 61 [3]. Mean plasma growth hormone climbed 2 to 10 fold for 6 days or more. IGF-I went up 1.5 to 3 fold and stayed elevated for 9 to 11 days. The half-life came out at 5.8 to 8.1 days, and with repeated exposure IGF-I held above baseline for up to 28 days. No serious adverse reactions, the authors noted. It’s the cleanest published look at how the albumin-bound form behaves over time.

CJC-1295 alongside a secretagogue

Plenty of protocols pair a GHRH analog with a growth hormone secretagogue like ipamorelin. Why? Different receptor entirely, the ghrelin receptor GHS-R1a [6]. Ipamorelin is a pentapeptide (Aib-His-D-2-Nal-D-Phe-Lys-NH2), and it was tagged as the first selective secretagogue, releasing growth hormone in rat pituitary cells with potency close to GHRP-6 but without the ACTH and cortisol bump the older peptides caused [7]. The reason to combine them is mechanistic, not hand-waving: switch on the GHRH receptor and the secretagogue receptor together and you get a cyclic AMP response roughly double what the GHRH receptor manages alone [5]. For the secretagogue half of that story, our GHRH versus GHRP overview walks through both receptor families.

How the three forms compare

Telling these peptides apart is mostly an analytical chemistry problem. Positional isomers of modified GRF(1-29) have been pulled apart and identified with chromatography plus mass spectrometry, which is how a lab confirms it’s holding the molecule it thinks it is [8]. For a related GHRH analog, our sermorelin overview goes deeper.

FAQ

Is CJC-1295 the same as Modified GRF (1-29)? Not really. Both are GHRH(1-29) analogs, but “CJC-1295” usually means the DAC form with the albumin-binding group. Modified GRF (1-29) has no anchor, so it clears far faster.

What does DAC change at the molecular level? It adds a maleimidopropionamide group that forms a covalent bond with Cys34 on serum albumin, stretching the peptide’s plasma presence from minutes to days [2].

Why do protocols add ipamorelin? It hits a separate receptor, and co-activating both gave a bigger cyclic AMP signal than either alone in a cell model [5].

References

1. Bai JP, Chang LL. The involvement of dipeptidyl peptidase IV in brush-border degradation of GRF(1-29)NH2 by intestinal mucosal cells. J Pharm Pharmacol. 1995. PMID 8583376
2. 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
3. Teichman SL, Neale A, Lawrence B, et al. 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. PMID 16352683
4. Prakash A, Goa KL. Sermorelin: a review of its use in the diagnosis and treatment of children with idiopathic growth hormone deficiency. BioDrugs. 1999. PMID 18031173
5. Cunha SR, Mayo KE. Ghrelin and growth hormone secretagogues potentiate GHRH-induced cyclic AMP production in cells expressing cloned GHRH and GHS receptors. Endocrinology. 2002. PMID 12446584
6. Howard AD, Feighner SD, Cully DF, et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science. 1996. PMID 8688086
7. Raun K, Hansen BS, Johansen NL, et al. Ipamorelin, the first selective growth hormone secretagogue. Eur J Endocrinol. 1998. PMID 9849822
8. Youn YS, Na DH, Yoo SD, Lee KC. Chromatographic separation and mass spectrometric identification of positional isomers of polyethylene glycol-modified growth hormone-releasing factor (1-29). J Chromatogr A. 2004. PMID 15633743