CJC-1295 in five numbers
- 30 residues: GHRH(1-29) plus one lysine
- 4 substitutions against enzymatic cleavage
- 5.8 to 8.1 d half-life in healthy adults
- 2 to 10× mean GH after one administration, for 6 days or more
- 1.5 to 3× IGF-1 after one administration, for 9 to 11 days
All five come from two papers, one in Endocrinology in 2005 and one in the Journal of Clinical Endocrinology and Metabolism in 2006 [2] [3]. The rest of the page is the story around them.
CJC-1295 with DAC or without
Two different molecules are sold as CJC-1295. The original, now called CJC-1295 with DAC, carries the albumin-binding linker and is the one tested in both human trials, with its week-long half-life [3]. The version without the linker, sold as CJC-1295 no DAC or Mod GRF 1-29, has the same four substitutions but no tail, so it is cleared within minutes and gives one GH pulse per administration. No human study of the linker-free peptide has been published. Table 1, at the top of the page, sets the two side by side.
The difference matters for anyone reading a certificate: the two forms have different masses and very different time scales, which is why research blends with ipamorelin use the linker-free one. The full comparison is in CJC-1295 DAC vs no DAC.
From a ConjuChem bench in Montreal
The starting material is the 1-29 fragment of human growth-hormone-releasing hormone, identified in 1982 as the shortest piece of the 44-residue hormone that retains full activity [1]. Its problem as a drug was always duration: the fragment is cut by dipeptidyl peptidase IV within minutes. ConjuChem's approach, described by Jetté and colleagues in 2005, was to make the peptide hitch a ride on the most abundant and longest-lived protein in blood. Serum albumin has one free thiol, cysteine 34; a maleimide group placed on a peptide reacts with it spontaneously in plasma.
The team synthesised three maleimido derivatives of a tetrasubstituted hGRF(1-29), conjugated each to human serum albumin, confirmed that the conjugates resisted dipeptidyl peptidase IV and still released GH from cultured rat pituitary cells, and gave them to rats. The best of the three, a version carrying an N-epsilon-3-maleimidopropionamide derivative of lysine at the C-terminus, produced four times the GH area under the curve of unmodified hGRF(1-29) over two hours, was still detectable in plasma beyond 72 hours, and appeared on Western blots riding on the albumin band from 15 minutes after administration. They named it CJC-1295 [2].
The four substitutions (D-Ala2, Gln8, Ala15, Leu27) are the same ones that define the linker-free peptide sold as Mod GRF 1-29. The linker is what "DAC" refers to, and its consequences are set out in DAC versus no DAC.
The first human trial: a week from one administration
Teichman and colleagues ran two randomized, placebo-controlled, double-blind, ascending-dose studies in healthy adults aged 21 to 61, at two sites, lasting 28 and 49 days. In the first, subjects received one of four single ascending study arms or placebo; in the second, repeated administration. After a single administration, mean plasma GH rose 2 to 10-fold depending on the arm and stayed elevated for 6 days or more; mean IGF-1 rose 1.5 to 3-fold and stayed elevated for 9 to 11 days.
After repeated administration, IGF-1 remained above baseline for up to 28 days. The estimated half-life was 5.8 to 8.1 days. No serious adverse reactions were reported, and the authors concluded that the peptide was safe and relatively well tolerated in that setting, with evidence of a cumulative effect after repeated administration [3].
Figure 6
What one CJC-1295 administration changed in the trial, and for how long (days)
- GH, single2-10×, 6+ days
- IGF-1, single1.5-3×, 9-11 days
- IGF-1, repeatedup to 28 days
The second: does a week-long signal flatten the pulses?
The physiological worry about a GHRH analogue that never goes away was that it would turn the pulsatile GH pattern into a plateau. Ionescu and Frohman answered it with the most direct experiment possible: healthy men aged 20 to 40 had blood drawn every 20 minutes for 12 hours overnight, received one administration in one of two study arms, and repeated the sampling night one week later. The pulses came back unchanged in frequency and in magnitude.
What changed was the baseline between them, 7.5-fold higher (P < 0.0001), and that raised trough accounted for a 46 % increase in mean GH and a 45 % increase in IGF-1. The two arms gave the same response, and the IGF-1 increase did not correlate with any single GH parameter [4]. Serum from 11 healthy young men, examined by two-dimensional electrophoresis before and one week after a CJC-1295 administration, showed the protein fingerprint of a raised GH/IGF-1 axis: an apolipoprotein A1 isoform and a transthyretin isoform down, beta-hemoglobin and albumin fragments up [6].
After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 d or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9-11 d.
What the mice added
One animal study belongs in the story because it tested the peptide where it would matter most: in mice with no GHRH gene at all. Alba and colleagues gave 1-week-old GHRH-knockout mice CJC-1295 at three different intervals for 5 weeks. The shortest interval normalised body weight and length; the longer ones improved them without full normalisation; relative lean and subcutaneous fat mass were normal in all treated groups.
The pituitaries of treated animals contained more total RNA and more GH mRNA, and immunohistochemistry showed more somatotroph cells, which the authors read as proliferation [5]. A mouse clears the albumin conjugate faster than a person, so the mouse data say nothing about people; the finding that matters is that a GHRH analogue could replace the missing hormone in an animal model.
The phase 2 that stopped
ConjuChem's clinical target was the same one tesamorelin later succeeded with: the visceral fat that accumulates in HIV patients on antiretroviral therapy. Trial GH100-013 (NCT00267527) was registered in December 2005 as a multicentre, randomized, placebo-controlled, double-blind phase 2 study of 120 patients receiving one of two CJC-1295 arms or placebo for 12 weeks with 6 weeks of follow-up.
Its status on the registry is "terminated", with a completion date of September 2006 and no results posted [7]. No later trial of CJC-1295 has been registered. The public record does not give the reason for the termination, and this site does not speculate. Tesamorelin, a different GHRH analogue, went on to a 412-patient trial and an approval; the contrast is drawn in CJC-1295 ipamorelin versus tesamorelin.
Afterlife under two names
A peptide that stops in phase 2 usually disappears. CJC-1295 did not, because its published human data were unusually clean and its synthesis is not difficult. It reappeared in the research-chemical market in two forms: the original albumin-binding molecule, sold as CJC-1295 DAC, and the linker-free intermediate, sold as CJC-1295 no DAC or Mod GRF 1-29, usually blended with ipamorelin. Neither is an approved drug.
The FDA's 2023 compounding decision placed ipamorelin acetate in category 2 and lists the CJC-1295 nomination among those later withdrawn [8]; the WADA Prohibited List names CJC-1295 among GHRH analogues in class S2 [9]. What the trials recorded by way of adverse events is on the CJC-1295 side effects page.
