CJC-1295 and DAC: the GHRH analog that anchors to albumin

Tying the peptide to albumin

Natural GHRH stimulates the pituitary to release growth hormone (GH), but its half-life is so short that it limits therapeutic use³. In the early 2000s, researchers at the Canadian company ConjuChem tried a chemical fix: add to the peptide a reactive group that, once in the blood, binds the free thiol of cysteine 34 on serum albumin. They called it the drug affinity complex (DAC)¹.

Of three maleimido derivatives of GHRH(1-29), the best was CJC-1295: a tetrasubstituted form of hGRF(1-29) with an added C-terminal lysine carrying the maleimidopropionamide group. In rats it produced a 4-fold larger GH area under the curve than hGRF(1-29) over 2 hours, remained in plasma beyond 72 hours, and appeared on the albumin band 15 minutes after injection¹. The four substitutions increase resistance to proteolytic degradation⁹. It is the component that the catalog's CJC-1295 + GHRP-6 Blend lists as "CJC-1295 (DAC)".

What the trial in healthy adults showed

The core human evidence comes from two randomized, double-blind, placebo-controlled ascending-dose trials in healthy subjects aged 21 to 61, lasting 28 and 49 days. After a single subcutaneous injection there were dose-dependent increases in plasma GH of 2- to 10-fold for 6 days or more and in IGF-1 of 1.5- to 3-fold for 9 to 11 days. The estimated half-life was 5.8 to 8.1 days².

With multiple doses, mean IGF-1 stayed above baseline for up to 28 days, with evidence of a cumulative effect. No serious adverse reactions were reported, and the authors described the compound as safe and relatively well tolerated, particularly at doses of 30 or 60 µg/kg². A later proteomic analysis in 11 healthy young men, before and one week after injection, identified serum protein changes that could serve as biomarkers of GH and IGF-1 action⁵.

Pulsatility: the key question

Pulsatile GH secretion is considered important for many of the hormone's physiological effects, and continuous stimulation could in theory flatten it. Ionescu and Frohman measured it with sampling every 20 minutes over 12 overnight hours in healthy men aged 20 to 40, before and one week after an injection. The frequency and magnitude of GH pulses did not change; what rose was basal GH between pulses, 7.5-fold (P < 0.0001), with mean GH up 46% and IGF-1 up 45%³.

In the laboratory, in mice lacking the GHRH gene, daily CJC-1295 for 5 weeks normalized body weight and length; at 48- or 72-hour intervals the effect was smaller and did not reach full normalization⁴. It is a useful nuance: a long half-life in humans does not guarantee that any interval reproduces physiology.

With DAC and without DAC: two molecules, one name

Two variants circulate under the name CJC-1295: the version with DAC and the "no-DAC" version, also called Mod GRF 1-29⁹. In 2009 a Norwegian anti-doping laboratory analyzed, at the request of Norwegian police and customs, an unknown preparation containing a 29-amino-acid peptide with a C-terminal amide, marketed as CJC-1295⁸, that is, without the extra lysine that carries the albumin anchor¹.

The difference is pharmacological, not a matter of labeling. The Teichman and Ionescu data belong to the DAC molecule²³. A 2026 review placed CJC-1295 without DAC in the lowest evidence tier, with no published human studies, and noted that its claimed effects are extrapolated from related compounds, chiefly GHRH(1-29), that is, sermorelin⁹.

The same logic that reached semaglutide

ConjuChem also applied the DAC platform to GLP-1: CJC-1131, a DPP-IV-resistant DAC:GLP-1 compound that conjugates to albumin, activated the GLP-1 receptor and lowered glucose in mice⁶. Using albumin as a carrier to prolong a peptide is the idea that, with different chemistry, underpins liraglutide and semaglutide: in those drugs albumin binding is reversible, through an optimized fatty acid and linker, not covalent as with DAC⁷. The full history of that strategy is in A century of peptide therapeutics.

2006: the trial that stopped

CJC-1295 advanced to a multicenter, randomized, double-blind, placebo-controlled phase 2 trial in HIV-associated visceral obesity, with 192 participants in North and South America and weekly injections. ConjuChem stopped the study on 17 July 2006 after a participant died at a site in Argentina; at the time, the cause and its relationship to the drug were under investigation¹⁰. In August 2006 the company posted the findings of that investigation, and the event cost it half of its share value¹¹.

The same indication did succeed with another GHRH analog. Tesamorelin, a once-daily GHRH(1-44), reduced visceral adipose tissue by 15.4% versus placebo in 806 patients with HIV, with no clinically meaningful changes in glucose at 26 and 52 weeks¹². The concept of stimulating the patient's own pituitary to reduce visceral fat was validated; what was never demonstrated was the weekly version.

Where the evidence ends

• The published human data are pharmacokinetic and pharmacodynamic, in healthy adults and short term; there are no controlled efficacy data on body composition or clinical outcomes²⁹.
• There are no long-term safety data, and concern about the mitogenic signal of raised IGF-1 remains theoretical, neither confirmed nor ruled out⁹.
• The clinical program was interrupted in 2006, so the molecule never completed a phase 3¹⁰.
• The no-DAC version has no human studies of its own⁹.

For the researcher, CJC-1295 remains a case of elegant design: it showed in humans that an albumin-anchored GHRH analog keeps GH and IGF-1 raised for days without losing the pulsatile pattern²³. The comparative picture of secretagogues, including ipamorelin and MK-677, is reviewed in CJC-1295, ipamorelin and MK-677.