CJC-1295 with DAC

CJC-1295 with DAC is a modified growth hormone releasing hormone fragment designed to associate with albumin, an abundant blood protein. Early human trials found prolonged increases in growth hormone (GH) and insulin-like growth factor 1 (IGF-1), while an overnight sampling study showed that GH pulses continued alongside higher hormone concentrations between pulses. Its development established sustained endocrine activity. Clinical benefits such as improved strength, recovery or long term health remain unresolved, and the available safety information includes reactions that require more attention than the early abstracts alone suggest.

Overview

The original development molecule combined a 29 residue GHRH core with substitutions at positions 2, 8, 15 and 27 and an additional modified lysine at the C terminus. The added maleimidopropionamide group permits covalent association with albumin. DAC stands for drug affinity complex. Jetté and colleagues (2005) described this albumin binding preparation in pituitary cell and rat experiments before the human pharmacology trials.

Molecular profile

Core: GHRH(1–29) analogue with four amino-acid substitutions Source
Core substitutions: D-alanine 2, glutamine 8, alanine 15 and leucine 27 Source
Additional residue and group: C terminal lysine bearing maleimidopropionamide, permitting albumin association Source
Molecular formula: C165H269N47O46, DAC free base before albumin association Source
Human study form: DAC peptide, counterion unspecified in published human accounts Source

Forms and derivatives

CJC-1295 no DAC / modified GRF(1–29)

The amidated 29 residue core has four substitutions and lacks the extra albumin binding unit. Published analytical studies characterize its identity and laboratory metabolism. The prolonged human hormone findings used DAC material.

DAC acetate and trifluoroacetate

These names describe counterions associated with the DAC peptide. FDA identifies trifluoroacetate in Jetté’s preclinical preparation, while the exact counterion in the human program was unspecified.

DAC, DAC free fragments and salt forms

The name CJC-1295 has also been applied to the 29 residue modified fragment without the added albumin binding unit, often called modified GRF(1–29) or CJC-1295 no DAC. These are materially different preparations. Acetate and trifluoroacetate identify counterions associated with a peptide; they do not indicate whether the DAC extension is present. The FDA assessment (2024) separates these identities and records that the exact salt form was unspecified in the human studies.

Uses and research areas

The human program examined whether a modified releasing hormone could sustain GH and IGF-1 after subcutaneous administration. Investigators measured circulating peptide, hormone concentrations and hormone secretion patterns in healthy adults. Those endpoints characterize pharmacology and provide a basis for further clinical development.

Animal research tested growth in mice lacking the GHRH gene, while exploratory human proteomics examined possible markers of GH action. Neither experiment measured healthy adult recovery, athletic function or longevity. There is no FDA approved CJC-1295 medicinal product, and the published healthy volunteer trials provide no established treatment indication.

Mechanism of action

The GHRH receptor on GH producing pituitary cells responds to the releasing hormone signal. CJC-1295 retains that receptor rationale while altering its exposure through sequence changes and the reactive extension. Albumin association increases the size of the circulating peptide complex and may protect it from some enzymatic breakdown. Jetté and colleagues demonstrated GH releasing activity of albumin conjugates in rat pituitary cells and found albumin associated material in rat plasma.

Exposure and hormone response can nevertheless diverge. In the rat experiments, GH returned toward baseline within hours while peptide remained detectable much longer, as detailed in the FDA's source specific assessment. Pituitary hormone stores, receptor responses and endocrine feedback can all influence secretion during persistent stimulation. The human studies therefore measured both peptide pharmacokinetics and GH or IGF-1 separately.

Pharmacokinetics

Teichman and colleagues (2006) reported an estimated CJC-1295 half-life of 5.8–8.1 days in two randomized ascending exposure trials. The trials involved healthy adults aged 21–61 and subcutaneous administration. This estimate concerns the circulating DAC preparation. Mean GH increased for at least six days after a single exposure, and mean IGF-1 for nine to eleven days. Repeated exposure produced a cumulative response, with IGF-1 remaining above baseline for as long as 28 days.

Those durations describe three different measurements: peptide elimination, GH response and IGF-1 response. The 5.8–8.1-day half-life range reflects estimates from the study's different exposure groups. Removing the DAC extension changes the molecule's protein association; the short half-life often attributed to modified GRF(1–29) cannot be obtained by subtracting part of the DAC molecule's duration.

Research findings

Pituitary activity and prolonged circulation in rats

Jetté and colleagues (2005) compared maleimido derivatives of the GHRH fragment, their albumin conjugates and the unmodified fragment. The conjugates resisted enzymatic degradation and stimulated GH release in cultured rat anterior pituitary cells. After subcutaneous administration in male Sprague Dawley rats, the selected CJC-1295 preparation produced an acute GH response and was detected in plasma beyond 72 hours. These experiments connect the chemical design to measured biological activity, while leaving the contribution of the sequence substitutions versus the DAC unit incompletely separated.

Hormone responses in healthy adults

Teichman and colleagues (2006) conducted two placebo controlled, double blind trials lasting 28 and 49 days. After single exposure, mean GH increased twofold to tenfold and mean IGF-1 by 1.5-fold to threefold, with effects lasting several days. The repeated exposure trial showed accumulation of endocrine effects. The report establishes prolonged hormone stimulation in selected healthy adults; its outcomes did not include physical function or disease prevention.

GH pulses and concentrations between pulses

Ionescu and Frohman (2006) compared overnight blood sampling before exposure and one week later in healthy young men. Twelve participants are identified in FDA's account of the study. GH pulse frequency and magnitude were unchanged, while the GH concentration between pulses (trough GH) rose 7.5-fold and the average GH concentration rose approximately 46%. The IGF-1 increase did not correlate with the assessed GH secretion parameters. Pulses therefore continued in the presence of higher background exposure. This combination explains why a preserved pulse pattern alone cannot establish unchanged endocrine physiology.

Growth in a missing signal mouse model

Alba and colleagues (2006) treated young mice lacking the GHRH gene for five weeks, comparing different exposure intervals with deficient mice given the carrying liquid without CJC-1295 and mice with one working copy of the GHRH gene (heterozygous controls). Growth improved, and one exposure condition normalized body weight and length. The animals began with an absent releasing signal, giving the analogue a defined deficiency to address. The findings concern restoration of growth in that genetic model, with pituitary changes consistent with increased GH production.

Exploratory protein markers and laboratory detection

Sackmann-Sala and colleagues (2009) examined serum from eleven men drawn from the earlier pulsatility cohort. Five protein spots changed, including albumin fragments and isoforms of transport proteins. The authors proposed candidate markers of GH action. This additional analysis extends the earlier physiology experiment to protein biomarkers; the same participants contribute to both reports, and the markers' clinical utility remains unvalidated.

Memdouh and colleagues (2021) separately studied breakdown products and detection of the DAC and DAC free preparations in laboratory systems and urine to which the researchers had added known peptides. The analytical separation supports careful material identification when interpreting research on similarly named compounds.

Safety and tolerability

Teichman's abstract reported no serious adverse reactions in its two early trials. The more detailed FDA assessment (2024) identifies local reactions, flushing, headache, gastrointestinal symptoms, transient low blood pressure and increased heart rate across the available healthy volunteer studies. The FDA's current safety summary also identifies immune reaction, impurity and ingredient characterization concerns involving compounded CJC-1295.

FDA records an unpublished phase 2 HIV lipodystrophy trial that ended after a participant suffered an acute myocardial infarction and died. The event's cause could not be established from the available report. It remains a consequential development event, while the absent full trial data limit conclusions about both efficacy and the frequency or causality of harms. Small healthy volunteer studies and short follow-up also leave delayed risks poorly characterized.

What the research means

The DAC development program succeeded in producing prolonged endocrine stimulation. Human observations showed sustained GH and IGF-1 changes, and overnight sampling explained how pulses could persist during increased overall exposure. The rat and mouse experiments add chemical and biological context to those measured human effects.

The next evidentiary step would be a patient outcome that matters beyond the hormone measurement, accompanied by adequate safety follow-up. The available studies do not establish that increasing IGF-1 improves health in adults who have no defined deficiency. They also leave the DAC free fragment's human pharmacology unresolved. Shared chemical ancestry identifies a useful comparison; it cannot determine equivalent benefits, exposure or harms.

FAQs

How long did the DAC peptide remain in circulation?

Teichman and colleagues (2006) reported an estimated 5.8–8.1 day half-life after subcutaneous administration in healthy adults. GH and IGF-1 response durations were separately measured. The estimate applies to the albumin binding preparation.

Were GH pulses preserved?

In healthy men, Ionescu and Frohman (2006) found that overnight GH pulses remained similar in frequency and size one week after CJC-1295 with DAC. The GH concentration between pulses increased 7.5-fold, and the average concentration rose approximately 46%, so continued pulses coexisted with higher background hormone levels.

Did the trials establish recovery or anti-aging benefits?

The healthy volunteer trials measured peptide exposure, GH and IGF-1. Their endpoints did not assess recovery, strength, functional decline or lifespan. A health benefit requires a relevant clinical outcome and adequate safety follow-up.

Is CJC-1295 no DAC equivalent?

The DAC free fragment lacks the modified lysine and reactive albumin binding unit. The FDA assessment (2024) explains that the DAC pharmacological profile cannot be extrapolated to it. Its exposure and effects need separate measurements.

What safety events were reported?

The detailed FDA assessment describes local reactions, flushing, headache, gastrointestinal symptoms, low blood pressure and increased heart rate. It also records a fatal myocardial infarction in an unpublished phase 2 trial; the available account cannot establish causality. Uncommon and delayed risks remain uncertain.

Does the mouse growth result apply to healthy adults?

Alba and colleagues (2006) studied young mice lacking the GHRH gene. The analogue addressed a missing releasing signal and improved growth in that model. Adult recovery and healthy aging involve different starting conditions and outcomes.

Modified GRF(1–29) shares the four substituted residues but lacks the albumin binding addition. Sermorelin retains the natural 29 residue sequence and has a historical childhood growth program. Tesamorelin modifies the full length releasing hormone and has a separate approved HIV lipodystrophy indication. Their profiles connect identity, exposure and measured outcomes within each development program.

References

Jetté L, Léger R, Thibaudeau K, Benquet C, Robitaille M, Pellerin I, Paradis V, van Wyk P, Pham K, Bridon DP. 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;146(7):3052–3058. DOI: 10.1210/en.2004-1286. PMID: 15817669.
Pituitary cell and rat experiments characterized GH releasing activity and prolonged circulation of albumin binding CJC-1295.
Teichman SL, Neale A, Lawrence B, Gagnon C, Castaigne JP, Frohman LA. 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. The Journal of clinical endocrinology and metabolism. 2006;91(3):799–805. DOI: 10.1210/jc.2005-1536. PMID: 16352683.
Two randomized healthy adult trials measured prolonged DAC peptide exposure and sustained GH and IGF-1 responses.
Ionescu M, Frohman LA. Pulsatile secretion of growth hormone (GH) persists during continuous stimulation by CJC-1295, a long-acting GH-releasing hormone analog. The Journal of clinical endocrinology and metabolism. 2006;91(12):4792–4797. DOI: 10.1210/jc.2006-1702. PMID: 17018654.
Overnight sampling found preserved pulses alongside increased trough and mean GH after DAC material.
Alba M, Fintini D, Sagazio A, Lawrence B, Castaigne JP, Frohman LA, Salvatori R. Once-daily administration of CJC-1295, a long-acting growth hormone-releasing hormone (GHRH) analog, normalizes growth in the GHRH knockout mouse. American journal of physiology. Endocrinology and metabolism. 2006;291(6):E1290–E1294. DOI: 10.1152/ajpendo.00201.2006. PMID: 16822960.
A five week experiment examined growth restoration in young mice lacking the GHRH gene.
Sackmann-Sala L, Ding J, Frohman LA, Kopchick JJ. Activation of the GH/IGF-1 axis by CJC-1295, a long-acting GHRH analog, results in serum protein profile changes in normal adult subjects. Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. 2009;19(6):471–477. DOI: 10.1016/j.ghir.2009.03.001. PMID: 19386527.
Serum proteomics proposed candidate markers using eleven participants from the earlier pulsatility cohort.
Memdouh S, Gavrilović I, Ng K, Cowan D, Abbate V. Advances in the detection of growth hormone releasing hormone synthetic analogs. Drug testing and analysis. 2021;13(11-12):1871–1887. DOI: 10.1002/dta.3183. PMID: 34665524.
Researchers studied the breakdown and detection of sermorelin, tesamorelin and CJC-1295 with and without DAC as separate peptides. They tested detection in urine after adding known peptides to it.
U.S. Food and Drug Administration. FDA Briefing Document: Pharmacy Compounding Advisory Committee Meeting, December 4, 2024. CJC-1295-related bulk drug substances. 2024.
Agency assessment separates DAC and DAC free identities and reviews pharmacology, human studies and safety.
U.S. Food and Drug Administration. Certain Bulk Drug Substances for Use in Compounding that May Present Significant Safety Risks. Accessed 13 October 2026.
CJC-1295 entry describes limited clinical data, immune and characterization concerns, increased heart rate and vasodilatory reactions.

Glossary

GHRH: Growth hormone releasing hormone, a hypothalamic peptide that stimulates GH producing pituitary cells.
IGF-1: Insulin-like growth factor 1, produced in liver and other tissues and mediating part of the GH response.
Pharmacokinetics: The study of how a compound enters, moves through and leaves the body.
Half-life: Time for an assayed concentration to fall by half during a specified disappearance or elimination phase.
Amidation: A chemical modification at the end of a peptide chain, indicated by NH2 in these names.
DAC: Drug affinity complex, the reactive addition enabling albumin association.
Albumin: An abundant circulating protein that can carry or bind other molecules.
Trough concentration: A lower concentration between hormone pulses or other peaks.
Proteomics: Study of proteins in a sample, including abundance and molecular forms.