What Has Published Research Reported About CJC-1295?

What is CJC-1295?

CJC-1295 is a synthetic analog of growth hormone-releasing hormone (GHRH), the hypothalamic peptide that signals the pituitary to release growth hormone (GH). It was first characterized in a 2005 paper in Endocrinology by Jetté, Léger, Thibaudeau and colleagues at ConjuChem, under the title “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” (source 3).

The design problem the authors set out to address was duration. Native GHRH is broken down quickly in plasma (source 2), so the goal was a GHRH analog that would stay active in circulation for days instead of minutes. The solution was to attach a reactive chemical group that lets the peptide bond to albumin, a circulating plasma protein, once it enters the bloodstream (source 3).

This profile summarizes what the published record reports about CJC-1295, from its chemical design through rodent studies and the small number of published studies in adult volunteers. Like every compound profile on the Steadfast Research Group blog, it covers literature only, written for researchers reviewing that literature.

Where does the GHRH sequence behind CJC-1295 come from?

GHRH was first isolated not from the hypothalamus but from a tumor. In 1982, Guillemin and colleagues reported in Science the isolation of a 44-amino-acid peptide with growth hormone-releasing activity from a human pancreatic tumor that had caused acromegaly, a condition of excess GH (source 1). The same report described two shorter related forms of 37 and 40 residues. The 44-residue form ended in an amidated C-terminus.

A second early finding explains why a long-acting analog was wanted at all. In 1986, Frohman, Downs and colleagues reported in the Journal of Clinical Investigation that human plasma rapidly degraded GHRH to a biologically inactive product cleaved at the amino terminus (source 2). In their in vitro plasma incubations, total GHRH immunoreactivity had a half-life of 63 minutes, and the cleaved product had lost its GH-releasing activity (source 2). That amino-terminal weak point became one of the targets of later analog design.

How was CJC-1295 built from GHRH(1-29)?

CJC-1295 starts from hGRF(1-29), the first 29 residues of the human sequence, and adds two kinds of change (source 3). The first is a set of four amino acid substitutions. The second is an extra lysine at the C-terminus whose side chain carries a 3-maleimidopropionamide group, the reactive handle that lets the peptide bond to albumin.

The four substitutions alone define the tetrasubstituted GRF(1-29) backbone. The maleimide-bearing lysine is what makes the molecule the compound the 2005 paper named CJC-1295 (source 3).

GHRH (also GRF or GRH)

Growth hormone-releasing hormone, first isolated as a 44-residue peptide in 1982 (source 1). Older papers use the names growth hormone-releasing factor (GRF) and GRH for the same peptide.

hGRF(1-29)

The first 29 amino acids of the human GHRH sequence, the fragment on which CJC-1295 is built (source 3).

Maleimide group

A thiol-reactive chemical group. In CJC-1295 it sits on the C-terminal lysine and was designed to bond to albumin (source 3).

Drug Affinity Complex (DAC)

The label attached to this albumin-bonding feature, as in the names “CJC-1295 with DAC” and “CJC-1295 without DAC.”

IGF-I

Insulin-like growth factor I, a hormone whose circulating level rises downstream of GH and was a main endpoint of the human studies (sources 4 and 5).

What did the 2005 rat study report?

Jetté and colleagues prepared several maleimide derivatives of hGRF(1-29) and first conjugated them to human serum albumin outside the body (source 3). All of the albumin conjugates were reported to be stable against dipeptidylpeptidase-IV in vitro and to remain bioactive in a GH secretion assay using cultured rat anterior pituitary cells.

The maleimide derivatives were then given subcutaneously to male Sprague-Dawley rats. CJC-1295 produced a larger GH area under the curve over the 2-hour sampling window than unmodified hGRF(1-29) (source 3). The authors also tracked the compound in plasma and reported a CJC-1295 immunoreactive species on the band corresponding to serum albumin, appearing after 15 minutes and still present in circulation beyond 24 hours (source 3). They concluded that CJC-1295 was a stable and active hGRF(1-29) analog with an extended plasma half-life.

What did the 2006 studies in adult volunteers measure?

Two papers published in the Journal of Clinical Endocrinology & Metabolism in 2006 report the human pharmacology of CJC-1295. Both are summarized here strictly as published literature.

The first, by Teichman, Neale, Lawrence, Gagnon, Castaigne and Frohman, combined two randomized, double-blind, placebo-controlled, ascending-level studies in adults aged 21 to 61 (source 4). After a single subcutaneous injection, mean plasma GH rose 2- to 10-fold for 6 days or more, and mean plasma IGF-I rose 1.5- to 3-fold for 9 to 11 days, with both increases scaling with the administered amount. The investigators estimated the half-life of CJC-1295 at 5.8 to 8.1 days. After repeated administration, mean IGF-I remained above baseline for up to 28 days (source 4).

For comparison, the in vitro plasma half-life the 1986 study reported for native GHRH immunoreactivity was 63 minutes (source 2). The albumin-bonding design moved that figure from about an hour to about a week, which is the central pharmacological fact of the CJC-1295 literature.

Did continuous stimulation change the pattern of GH release?

A long-acting GHRH signal raises an obvious question: does GH secretion lose its normal pulsatile pattern when the stimulus never switches off? Ionescu and Frohman addressed this in the second 2006 paper (source 5). They sampled blood every 20 minutes over an overnight 12-hour period in men aged 20 to 40, before and one week after a single injection at one of two levels.

The authors reported that the frequency and magnitude of GH secretory pulses were unaltered (source 5). What changed was the floor between pulses: trough GH rose about 7.5-fold (p < 0.0001), mean GH rose 46 percent and IGF-I rose 45 percent, with no significant difference between the two levels studied. The IGF-I increase did not correlate with any individual parameter of pulsatile GH secretion, and the authors concluded that the marked rise in trough GH was an important route to the higher IGF-I (source 5).

What did the GHRH knockout mouse study observe?

Alba, Fintini, Sagazio and colleagues, with Salvatori as senior author, tested CJC-1295 in mice lacking the GHRH gene (GHRHKO mice) in a 2006 paper in the American Journal of Physiology: Endocrinology and Metabolism (source 6). The authors noted their earlier finding that even twice-daily injections of a conventional GHRH analog had not normalized growth in these mice. Because mouse albumin has a half-life of about 1 day, they compared three administration intervals: every 24, 48 or 72 hours.

Three groups of 1-week-old GHRHKO mice received CJC-1295 for 5 weeks, with placebo GHRHKO mice and heterozygous littermates as controls (source 6). Mice on the 24-hour interval reached normal body weight and length. Mice on the 48- and 72-hour intervals reached higher weight and length than placebo animals, without full normalization. Femur and tibia length stayed normal at the 24- and 48-hour intervals, and relative lean mass and subcutaneous fat mass were normal in all groups that received CJC-1295. The authors also reported increased total pituitary RNA and GH mRNA, and immunohistochemistry consistent with proliferation of GH-producing somatotroph cells (source 6).

What did proteomic research add?

A 2009 study in Growth Hormone & IGF Research by Sackmann-Sala, Ding, Frohman and Kopchick used CJC-1295 as a tool rather than a subject (source 7). The goal was to find new serum markers of GH and IGF-I action, since the established markers vary widely between individuals. Serum from 11 young adult men was collected before and one week after a CJC-1295 injection and analyzed by two-dimensional gel electrophoresis, with changed protein spots identified by mass spectrometry.

Two spots decreased, identified as an apolipoprotein A1 isoform and a transthyretin isoform. Three spots increased, containing beta-hemoglobin, a C-terminal fragment of albumin, and a mixture of an immunoglobulin fragment with another C-terminal albumin fragment (source 7). The authors described these as potential biomarkers of GH and IGF-I action and stated that the mechanisms linking them to GH activity remained to be clarified.

How do the published CJC-1295 studies compare?

What remains unresolved in the CJC-1295 literature?

The peer-reviewed record is small and concentrated in 2005 to 2009. The human data come from short studies in adult volunteers (sources 4, 5 and 7), two of which enrolled men only (sources 5 and 7), and the only growth study was in a knockout mouse model (source 6). The 2005 paper reported its in vivo GH result over a 2-hour window in rats (source 3), so the multi-day pharmacology rests on the 2006 human studies. None of the figures in this post should be read as applying beyond the conditions of the studies that produced them.

The naming also needs care. The published studies summarized here describe the maleimide-bearing molecule that bonds to albumin (sources 3, 5 and 6). Material labeled “CJC-1295 without DAC” refers to the tetrasubstituted GRF(1-29) backbone without that lysine-maleimide handle, so findings from the albumin-bonding studies, especially the multi-day half-life, do not transfer to it automatically.

For laboratories, that structural distinction is the practical point. Because the two forms differ by a defined C-terminal modification, confirming identity against the expected structure by mass spectrometry matters alongside an HPLC purity figure. The CJC-1295 / Ipamorelin blend page sets out the identity and Certificate of Analysis details for the related catalog material, and the companion profile on what published research has reported about ipamorelin covers the other peptide in that blend.