CJC-1295 (with DAC)
CJC-1295 DAC, DAC:GRF, GRF(1-29) drug affinity complex conjugate, tetrasubstituted GRF(1-29)-Lys30-MPA
CJC-1295 with DAC is a synthetic 30-amino-acid analogue of growth hormone-releasing hormone that is chemically engineered to latch onto albumin in the bloodstream, giving it a half-life of roughly a week rather than minutes. A single injection keeps growth hormone and IGF-1 elevated for days. It has never been approved anywhere for any purpose: its clinical development was abandoned in 2006 after a phase 2 trial was halted, and no efficacy trial has ever been published.
Mechanism
CJC-1295 is a modified version of GRF(1-29), the shortest fragment of human growth hormone-releasing hormone that retains full biological activity. It binds the GHRH receptor, a class B G-protein-coupled receptor found on pituitary somatotrophs. Occupancy couples to Gs, raises intracellular cAMP, activates protein kinase A and the transcription factor CREB, and drives two things at once: immediate release of stored growth hormone, and transcription of the GH1 gene plus somatotroph proliferation. Because the compound acts upstream of the pituitary rather than replacing growth hormone itself, its output remains subject to the brakes the body already has in place: hypothalamic somatostatin tone and negative feedback from circulating IGF-1. That is why growth hormone continues to be released in discrete pulses even under continuous stimulation, and why the achievable peak is capped by pituitary reserve rather than by dose.
Two separate engineering changes distinguish it from the native hormone. First, four amino acid substitutions (D-Ala2, Gln8, Ala15, Leu27). D-Ala2 blocks cleavage by dipeptidyl peptidase-4 at the N-terminus; Gln8 replaces a deamidation-prone asparagine and Leu27 an oxidation-prone methionine, removing two chemical liabilities; Ala15 replaces glycine and stabilises the helical conformation of the peptide. Second, a lysine is appended at position 30 carrying a maleimidopropionyl group, the so-called drug affinity complex. This maleimide reacts selectively and covalently with the single free thiol of Cys34 on circulating human serum albumin, so within minutes of injection the peptide becomes a bioconjugate riding on a 67 kDa carrier protein that is protected from renal filtration and recycled by the neonatal Fc receptor. That covalent conjugation, not the amino acid substitutions, is what converts a pharmacological pulse lasting minutes into a continuous elevation of GHRH-receptor tone lasting days. It is also the compound's central theoretical liability: sustained rather than episodic stimulation of the somatotroph, with IGF-1 held above baseline continuously, is a physiologically unnatural state whose long-term consequences have never been studied in humans.
What the research shows
There are exactly two published human studies of CJC-1295, both from 2006 and both sponsored by the developer. Teichman and colleagues ran two randomised, placebo-controlled, double-blind ascending-dose trials in healthy adults lasting 28 and 49 days. Single doses produced dose-dependent increases in mean growth hormone concentrations of 2- to 10-fold for six days or more, and IGF-1 increases of 1.5- to 3-fold sustained for 9 to 11 days; the estimated terminal half-life was 5.8 to 8.1 days. Multiple doses maintained IGF-1 above baseline throughout. Ionescu and Frohman then used frequent blood sampling to show that pulsatile growth hormone secretion was preserved after a single injection: basal (trough) growth hormone concentrations rose about 7.5-fold, but pulse frequency was unchanged, and the rise in IGF-1 tracked trough and mean growth hormone rather than pulse amplitude. In animals, once-daily CJC-1295 fully normalised growth in GHRH-knockout mice, while 48- and 72-hour dosing intervals produced only partial correction.
That is the whole human evidence base, and it is worth being blunt about what it does not contain. Every one of those endpoints is a biomarker. No published trial has ever measured whether CJC-1295 changes body composition, muscle strength, bone density, sleep, recovery from injury, or any clinical outcome in humans. The phase 2 trial that would have answered such questions (a multicentre, randomised, placebo-controlled study of 192 people with HIV-associated visceral adiposity) was halted in July 2006 after a participant at a site in Argentina died following a myocardial infarction. The attending physician attributed the death to pre-existing, asymptomatic coronary artery disease and judged it unrelated to treatment, but the sponsor terminated the programme regardless and the trial results were never published. That account rests on the sponsor's contemporaneous statements and press reporting rather than on any peer-reviewed adjudication. No sponsor has resumed development in the two decades since. Everything sold and discussed as CJC-1295 today rests on two short biomarker studies in healthy volunteers and an abandoned development file.
Evidence assessment
Limited evidence
Human data consist of two small, short, sponsor-run pharmacodynamic studies in healthy volunteers measuring only growth hormone and IGF-1; the only other citation is a mouse study, no efficacy trial has ever been completed or published, and the single phase 2 trial was halted and never reported.
Tiers are applied consistently across the library and re-checked when new trials read out. Read the grading method.
Key studies
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 Limited evidence
Single doses raised mean GH 2- to 10-fold for six days or more and IGF-1 1.5- to 3-fold for 9 to 11 days, with an estimated half-life of 5.8 to 8.1 days.
Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog Limited evidence
GH pulsatility was preserved during sustained GHRH-receptor stimulation, with basal (trough) GH increased roughly 7.5-fold and pulse frequency unchanged; the IGF-1 rise tracked trough and mean GH rather than pulse amplitude.
Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse Preclinical only
Daily dosing restored normal body weight and length; 48- and 72-hour intervals produced partial growth improvement only.
Safety
No long-term human safety data exist. The two published trials reported injection-site reactions, flushing and headache as the common findings over 28 to 49 days, with no serious drug-related events, but 49 days in healthy volunteers cannot characterise the risk profile of a compound designed to hold IGF-1 elevated indefinitely. The class hazards are inferred from growth hormone and from tesamorelin's approved labelling: fluid retention, arthralgia, carpal tunnel symptoms, impaired glucose tolerance and frank diabetes, and a theoretical concern about neoplasia driven by sustained IGF-1 elevation. Because CJC-1295 stimulates the pituitary rather than replacing growth hormone, an intact somatostatin brake limits acromegalic overshoot, but this has never been formally tested over months or years. The 2006 phase 2 death, whatever its true cause, was never publicly adjudicated in a peer-reviewed report. Separately, material bought outside a regulated supply chain carries risks that have nothing to do with the molecule: unverified identity and purity, bacterial endotoxin, and residual synthesis reagents.
Regulatory status
| Jurisdiction | Status |
|---|---|
| United Kingdom | No UK marketing authorisation. Supplying CJC-1295 for human use is unlawful under the Human Medicines Regulations 2012. It is sold in the UK as a laboratory research chemical; supplying it with dosing or injection instructions is treated by the MHRA as marketing an unlicensed medicine. |
| United States | Not approved by the FDA for any indication and never was. CJC-1295 is not on Category 1 of the FDA's interim 503A bulk drug substances list, so it cannot lawfully be used in pharmacy compounding for humans; FDA has grouped it with peptides it considers to raise significant safety concerns, and that categorisation has been contested in litigation brought by compounding interests. Material sold online is labelled 'for research use only', a phrase that carries no FDA sanction and functions mainly as a legal shield permitting the sale of an unapproved drug to consumers. |
| WADA (sport) | Prohibited at all times, in and out of competition, under section S2.2.4 of the WADA Prohibited List (growth hormone releasing factors), which names CJC-1295 explicitly among prohibited GHRH analogues. |
Questions
No. CJC-1295 has never been approved by the FDA or any other regulator, for any indication, in any country. Its clinical development was abandoned in 2006 and never restarted. It is also not permitted for use in pharmacy compounding for humans in the US.
They are chemically different molecules. Both share the same four amino acid substitutions to the GRF(1-29) backbone, but the DAC version carries an extra lysine at position 30 with a maleimidopropionyl group that binds covalently to albumin. That single addition changes the half-life from minutes to roughly a week. The two published human trials were conducted with the DAC version; the non-DAC version has no published human trial of its own.
No published human study has ever measured muscle mass, strength or body composition on CJC-1295. The only human data are two short trials in healthy volunteers measuring growth hormone and IGF-1 in blood. Elevated IGF-1 is a biomarker, not an outcome, and the leap from one to the other has not been tested.
A phase 2 trial in HIV-associated visceral fat accumulation, with 192 participants enrolled, was halted in July 2006 after a participant died following a myocardial infarction. The trial physician attributed the death to pre-existing asymptomatic coronary artery disease and considered it unrelated to the drug, but the sponsor ended the programme anyway. The trial results were never published, no peer-reviewed adjudication of the death exists, and no company has picked the compound up since.